Docket Number EPA-HQ-OPP-2012-0794 

www.regulations.gov 

Chlorinated Isocyanurates 

Amended Final Work Plan 

Registration Review 

Case Number 0569 

February 2014 

Approved by: 

Susan Lewis 

Director 

Antimicrobials Division 

Date: 
Docket Number EPA-HQ-OPP-2012-0794 

www.regulations.gov 

2 

Chlorinated Isocyanurates Amended Final Work Plan

Introduction

This document amends the Final Work Plan (FWP) for the registration review of chlorinated 

isocyanurates. Since the publication of the June 2013 Final Work Plan, the Agency has 

determined that certain data requirements identified to support the registration review of 

chlorinated isocyanurates were inadvertently omitted in the FWP. This document amends the 

June 2013 FWP to include the following study among the data identified as needed for 

registration review: 

 850.1035 Acute marine/estuarine invertebrate toxicity (shrimp) 

Additionally, the guideline number for the Indoor Exposure, Inhalation study was incorrectly 

listed as 875.1300. It should be listed as 875.1400. 

Finally, in response to the Isocyanurates Industry Ad Hoc Committee (IIAHC) request for a copy 

of the full list of chlorinated isocyanurate products/uses derived from labels, EPA has placed the 

“AD Label Data Report Chlorinated Isocyanurates” report for PC codes 081404, 081405, 081407 

in the docket for this case. Thus, this document amends EPA’s response to comment 13 of the 

June 2013 FWP. 

Unless otherwise stated by the Agency, all other elements of the Agency's June 2013 chlorinated 

isocyanurates FWP remain unchanged. 

Summary of Data Requirements

A summary table of the data required to support the registration review of chlorinated 

isocyanurates is presented below. 

Data Requirements for the Registration Review of Chlorinated Isocyanurates 

OCSPP GLN Study Name Test 

Substance

Time 

Frame 

(Months 

from 

DCI 

Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) 

Triggering Data 

Requirement

Applicable Exposure 

Scenarios

875.1400 Indoor Exposure, 

Inhalation 

Degradate 

(isocyanuric 

acid) 

24 

Occupational and 

Residential 

Handler 

All See notes 1, 2, 3 and 4. 

875.1700 Product Use 

Information TGAI 12 All All All above scenarios. 

875.2300 Indoor Surface 

Residue Dissipation TGAI 24 Residential Household floors5

 Toddlers playing on 

disinfected floors 

850.1010 Aquatic invertebrates, 

acute, freshwater 

Degradate 

(isocyanuric 

acid) 

24 Aquatic organisms All6 Transport to the aquatic 

environment 
Docket Number EPA-HQ-OPP-2012-0794 

www.regulations.gov 

3 

OCSPP GLN Study Name Test 

Substance

Time 

Frame 

(Months 

from 

DCI 

Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) 

Triggering Data 

Requirement

Applicable Exposure 

Scenarios

850.1025 or 

850.1055 

Estuarine/marine acute 

mollusk (shell 

deposition or 

embryo/larvae test) 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1035 

Acute marine/estuarine 

invertebrate toxicity 

(shrimp) 

Degradate 

(isocyanuric 

acid) 

24 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1075 

Fish acute, freshwater 

(warm and cold water 

species7) 

Degradate 

(isocyanuric 

acid) 

18 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1075 Fish acute, 

estuarine/marine 

Degradate 

(isocyanuric 

acid) 

18 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1300 Freshwater 

invertebrate life cycle 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1350 Estuarine/marine 

invertebrate life cycle 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.14008

Fish early life-stage, 

freshwater or 

estuarine/marine 

species 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.41009

Seedling emergence, 

Tier II – dose 

response, rice 

Degradate 

(isocyanuric 

acid) 

12 Aquatic/Terrestrial 

exposure and risk 

All6

 except in-can 

material preservatives 

and floriculture patch 

Transport to the aquatic 

environment 

850.41509 Vegetative vigor, Tier 

II – dose response, rice 

Degradate 

(isocyanuric 

acid) 

12 

Aquatic/Terrestrial 

organism exposure 

and risk 

All6

 except in-can 

material preservatives 

and floriculture patch 

Transport to the aquatic 

environment 

850.440010 

Aquatic Plant Testing 

using Lemna sp., Tier 

II 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.450011 

Algal Toxicity Tier II 

–marine diatom, 

freshwater diatom, 

green algae 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.455011 Algal Toxicity Tier II - 

Cyanobacteria 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

835.1230 (or 

OECD 106) Batch Equilibrium 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6 Transport and fate to the 

aquatic environment 

835.311012 Ready 

Biodegradability 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

835.322012 Porous Pot Test 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 
Docket Number EPA-HQ-OPP-2012-0794 

www.regulations.gov 

4 

OCSPP GLN Study Name Test 

Substance

Time 

Frame 

(Months 

from 

DCI 

Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) 

Triggering Data 

Requirement

Applicable Exposure 

Scenarios

835.324012 

Simulation Test – 

Aerobic Sewage 

Treatment: A. 

Activated Sludge Units 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

835.328012 

Simulation Test to 

Assess the 

Biodegradability of 

Chemicals Discharged 

to wastewater 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

835.4300 Aerobic aquatic 

metabolism 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6 Transport to the aquatic 

environment 

835.4400 Anaerobic aquatic 

metabolism 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6 Transport to the aquatic 

environment 

OECD 209 or 

850.330013 

Activated Sludge 

Respiration Inhibition 

(ASRI) 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

860.146014 Food-handling TEP 24 Dietary and 

aggregate risk 

Food processing, 

dairy, and public 

eating establishments 

Dietary 

Special Study15 Migration studies TEP 24 Dietary and 

aggregate risk 

Adhesives and 

pulp/paper mill 

slimicide use 

Dietary 

OCSPP: Office of Chemical Safety and Pollution Prevention; GLN: guideline number; DCI: data call-in 

1 Applicable Occupational Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for hard surface 

disinfection and pool treatment; 2- Open pour granules for material preservation; 3- Mop, wipe and trigger spray for 

hard surface disinfection; 4- Hand wand spray disinfection of egg and food processing plants; 5- Fogging 

disinfection of egg and food processing plants; and 6- Brush, roller and spray application of preserved paints. 

2 Applicable Residential Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for pool treatment; 

2- Mop, wipe and trigger spray for hard surface disinfection; and 3- Brush, roller and spray application of preserved 

paints. 

3 It may be possible to use proprietary surrogate exposure data if data compensation issues can be addressed. 

4 If the labels are modified to require automatic foggers in place of hand held foggers, then the study of hand held 

fogging exposures would not be expected to be needed. 

5 If surface residue data are not available, then the standard assumption of 100 percent transferable surface residue 

will be used which might overestimate the risk. For Hard Surface Flooring, only. 

6

 Industrial Process and Water Treatment: Cooling Tower and Swimming Pools and Water Beds; Hard Surfaces 

Disinfectants and Sanitizers: Down-the-Drain (DtD) residential and industrial; Laundry Products: DtD residential 

and commercial; Material Preservatives: DtD Production and In-Service. 

7 Except for the industrial processes and water system uses, testing of a second freshwater species (cold or warm 

water) may be waived if isocyanuric acid is not stable and the median lethal concentration (LC50) in the first species 

tested is >1 ppm. 

8 Expected to be required for the more acutely sensitive of the freshwater and estuarine/marine fish species tested. 

9 Data may be waived for uses where environmental exposure concentrations will be less than the aquatic plant 

growth Tier II (850.4400, 850.4500, and 850.4550) no observable adverse effect concentration (NOAEC) values. 
Docket Number EPA-HQ-OPP-2012-0794 

www.regulations.gov 

5 

10 Except for industrial process and water treatment uses, a use may be eligible for data waiver if the aquatic plant 

NOAEC results are all greater than or equal to 1 ppm. 

11 All uses footnoted with marine diatom and freshwater diatom data for material preservative uses, hard surface 

disinfection and sanitization uses, and floriculture use may be eligible for data waiver if green algae (Selenastrum 

capricornutum) NOAEC results are greater than or equal to 1 ppm. The anticipated DCI will address this. 

12 EPA has published final guidelines for four biodegradation studies. The biodegradation study anticipated to be 

required for chlorinated isocyanurates is for the degradate (Cyanuric acid based on an Activated Sludge Respiration 

Inhibition Test. The Agency anticipates codifying these studies in 40CFR 158W in the near future. 

13 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine 

which of these four biodegradation tests would be anticipated to be required. If the ASRI test EC50 is less than or 

equal to 20 milligrams per liter (mg/L), then either the (i)Biodegradation in Activated Sludge Study or (ii) 

Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test would be 

anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then the DCI expected to be issued would 

provide that the registrant would choose to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in 

Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous 

Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to 

be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in 

Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous 

Pot study would be expected to be required. The appropriate Test Substance to satisfy the guideline requirement is 

the degradate (cyanuric acid). 

14 Residue chemistry data are anticipated to be needed to determine dietary exposure to cyanuric acid/isocyanuric 

acid following sanitization of food contact surfaces of food processing plants (including dairies) and food-handling 

facilities (including public eating places). Protocol submission is recommended. The anticipated DCI will address 

this. 

15 Migration of cyanuric acid/isocyanuric acid from preserved adhesive to food and from paper/paperboard to food 

following the slimicide use. The anticipated DCI will provide that a protocol must be submitted for EPA approval 

prior to initiating the study. 

Page 2 of 80

Table of Contents

1 Introduction ............................................................................................................................. 5

1.1 Statutory and Regulatory Authority ................................................................................. 5

1.2 Updates to the Work Plan ................................................................................................. 7

1.3 Case Overview ................................................................................................................. 8

1.4 Chemical Identification and Properties ............................................................................ 9

1.5 Use/Usage Description ................................................................................................... 11

1.5.1 Registrations ........................................................................................................... 11

1.5.2 Summary of Registered Uses .................................................................................. 11

1.5.3 Usage Information .................................................................................................. 13

1.6 Regulatory History ......................................................................................................... 14

1.6.1 Recent/Pending Regulatory Actions ....................................................................... 14

1.6.2 Tolerance Information ............................................................................................ 14

1.7 Incidents ......................................................................................................................... 14

1.7.1 Human Health ......................................................................................................... 14

1.7.2 Ecological ............................................................................................................... 15

2 Anticipated Data Needs ........................................................................................................ 15

3 Human Health Risk Assessment ........................................................................................... 19

3.1 Existing Toxicological Endpoints .................................................................................. 19

3.2 Dietary Exposure ............................................................................................................ 20

3.2.1 Food ........................................................................................................................ 20

3.2.2 Drinking Water ....................................................................................................... 21

3.3 Occupational and Residential (ORE) Exposures ........................................................... 21

3.3.1 ORE Exposure Assessed in the RED ...................................................................... 21

3.3.2 ORE Exposures Assessed after the RED ................................................................ 22

3.3.3 ORE Exposures that will Need to Be Assessed for Registration Review ............... 22

3.4 Aggregate and Cumulative Exposure ............................................................................. 23

3.4.1 Aggregate Exposures .............................................................................................. 23

3.4.2 Cumulative Exposures ............................................................................................ 23

4 Environmental Risk Assessment........................................................................................... 23

4.1 Environmental Conceptual Model Exposure Pathways ................................................. 23
Page 3 of 80

4.2 Ecological Effects Assessment ....................................................................................... 28

4.2.1 Mechanism of Action .............................................................................................. 28

4.2.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 29

4.3 Exposure Analysis Plan .................................................................................................. 30

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates ............................................ 30

4.3.2 Down-the-Drain Analysis ....................................................................................... 30

4.4 Effects Analysis Plan ..................................................................................................... 31

5 Endocrine Disruptor Screening Program (EDSP) ................................................................. 31

6 Next Steps ............................................................................................................................. 32

7 References ............................................................................................................................. 32

Appendix A: Environmental Fate ................................................................................................. 35

Appendix B: Toxicology Profile ................................................................................................... 44

Appendix C: Ecotoxicology Profile .............................................................................................. 46

Appendix D: ECOSAR Version 1.1 Results Page for Isocyanuric Acid ...................................... 56

Appendix E: Response to the 60-Day Public Comments on the Chlorinated Isocyanurates ........ 58

List of Tables 

Table 1 - Summary of Anticipated Risk Assessments and Data Needs ......................................... 6

Table 2 - Anticipated Registration Review Schedule ..................................................................... 7

Table 3 - Chemical Identification Information for the Chlorinated Isocyanurates ......................... 9

Table 4 – Physical and Chemical Properties for the Chlorinated Isocyanurates .......................... 10

Table 5 - Distribution of Products by Specific Chlorinated Isocyanurate .................................... 11

Table 6 – Summary of Chlorinated Isocyanurate Antimicrobial Uses ......................................... 12

Table 7 - Incidents Reported for the Chlorinated Isocyanurates .................................................. 15

Table 8 - Studies Anticipated as Needed for the Registration Review of the Chlorinated 

Isocyanurates................................................................................................................................. 16

Table 9 – Existing Toxicology Endpoints .................................................................................... 19

Table 10 - ORE Scenarios for the Chlorinated Isocyanurates ...................................................... 22

Table 11 – Existing Ecological Effects Endpoints ....................................................................... 29

Table 12 Environmental Fate Data for Chlorinated Isocyanurates (di- and tri-chloro) ............... 38

Table 13 - Acute Toxicity of the Chlorinated Isocyanurates ........................................................ 44

Table 14 Available Endpoints from Avian Ecotoxicity Studies for Trichloro-s-triazinetrione ... 46

Table 15 Available Endpoints from Avian Ecotoxicity Studies for Sodium Dichloroisocyanurate 

Dihydrate....................................................................................................................................... 47
Page 4 of 80

Table 16 Available Endpoints from Avian Ecotoxicity Studies for Sodium Dichloro-sTriazinetrione ................................................................................................................................ 47

Table 17 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate Ecotoxicity 

Studies for Trichloro-s-triazinetrione ........................................................................................... 50

Table 18 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate Ecotoxicity 

Studies for Sodium Dichloro-s-Triazinetrione .............................................................................. 51

Table 19 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate Ecotoxicity 

Studies for Sodium Dichloroisocyanurate Dihydrate ................................................................... 51

Table 20 Available Avian Acute Toxicity Studies for Isocyanuric Acid .................................... 53

Table 21 - Available Aquatic Organism data for Isocyanuric Acid ............................................. 53

List of Figures 

Figure 1 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates 

and their Reaction Products/Degradates from Sanitizing and Disinfecting Uses for Laundry and 

Hard Surfaces to Aquatic and Terrestrial Organisms ................................................................... 25

Figure 2 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates 

and their Reaction Products/Degradates from Swimming Pool and Water Bed Uses to Aquatic 

and Terrestrial Organisms ............................................................................................................. 26

Figure 3 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates 

and their Reaction/Degradates from Cooling Water Tower Uses to Aquatic and Terrestrial 

Organisms ..................................................................................................................................... 27

Figure 4 Conceptual Model for Ecological Exposure and Effects of Chlorinated Isocyanurates 

and their Reaction/Degradates from the Use and Disposal of In-Can or In-Container Material 

Preservatives to Aquatic Organisms ............................................................................................. 28

 
Page 5 of 80

1 Introduction 

1.1 Statutory and Regulatory Authority 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States generally must be registered by the U.S. 

Environmental Protection Agency (USEPA, EPA, or the Agency) based on scientific data 

showing that they will not cause unreasonable risks to human health or the environment when 

used as directed on product labeling. The registration review program is intended to make sure 

that, as the ability to assess risk evolves and as policies and practices change, all registered 

pesticides continue to meet the statutory standard of no unreasonable adverse effects to human 

health or the environment. Changes in science, public policy, and pesticide use practices will 

occur over time. Through the registration review program, the Agency periodically reevaluates 

pesticides to make sure that as change occurs, products in the marketplace can be used safely. 

Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The Agency 

will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. The 

Chlorinated Isocyanurates Preliminary Work Plan (PWP) was published on December 21, 2012, 

and the 60-day comment period ended on February 21, 2013. 

Documents associated with this registration review can be viewed at www.regulations.gov in 

docket EPA-HQ-OPP-2012-0794. Below is a summary of the issues relevant to this registration 

review case. 

 
Page 6 of 80

Table 1 - Summary of Anticipated Risk Assessments and Data Needs 

Risk Assessment 

Assessment 

Necessary to 

Support 

Registration 

Review 

Date of Most 

Recent 

Assessment 

Type of 

Assessment 

Required 

(New/Updated) 

Data Needed 

Dietary (food) Yes None New Food-handling, Migration 

Studies1

Dietary (drinking water) Yes 3/26/2001 Updated None 

Occupational Handler 

(Inhalation Exposure) Yes None New Inhalation Indoor Exposure Data2 

Residential Handler 

(Inhalation Exposure) Yes None New Inhalation Indoor Exposure Data3 

Residental Post Application, 

Swimming Pools 

(Incidental Oral Exposure) 

Yes 2/26/2001 Updated None 

Residental Post Application, 

Disinfected Floors 

(Incidental Oral Exposure) 

Yes None New Surface Residue Data 

Aggregate Exposures Yes None New None 

Cumulative Exposures No None None None 

Ecological Yes None4 New 

Isocyanuric acid/cyanuric acid 

acute and chronic data for 

freshwater fish and 

invertebrates and 

estuarine/marine fish and 

invertebrates, Aquatic plants 

vascular and non-vascular, 

Vegetative vigor and seedling 

emergence tests with rice, 

ASRI, Aquatic metabolism, 

WWTP biodegradation study

1. Residue chemistry data are anticipated as needed to determine dietary exposure to cyanuric acid/isocyanuric acid following 

sanitization of food contact surfaces of food processing plants (including dairies) and food-handling facilities (including public 

eating places), adhesive preservation, and slimicide use in the pulp slurry to make paper/paperboard for food contact. 

2. Indoor exposure data are anticipated as needed for the following occupational handler scenarios: 1- Open pour liquids, 

granules and powder for hard surface disinfection and pool treatment; 2- Open pour granules for material preservation; 3- Mop, 

wipe and trigger spray for hard surface disinfection; 4- Hand wand spray disinfection of egg and food processing plants; 5- 

Fogging disinfection of egg and food processing plants; and 6- Brush, roller and spray application of preserved paints. 

3. Indoor exposure data are needed for the following residential handler scenarios: 1- Open pour liquids, granules and powder for 

pool treatment; 2- Mop, wipe and trigger spray for hard surface disinfection; and 3- Brush, roller and spray application of 

preserved paints. 

4. A hazards assessment was done in the 1992 RED, but no risk assessment was conducted. 
Page 7 of 80

Table 2 - Anticipated Registration Review Schedule 

Anticipated Activity Target Date1 Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Public Comment for Preliminary Work 

Plan 2012-12 2012-12-19 

Close Public Comment Period 2013-02 2013-02-21 

Phase 2: Case Development 

Issue Final Work Plan 2013-06 2013-06-28 

Issue Data Call-In (DCI) 2014-06 

Receive Data to be Considered in Risk Assessment 2016-06 

Open 30-Day Public Comment Period for Preliminary Risk 

Assessment(s) 2017-12 

Close Public Comment Period 2018-01 

Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2018-06 

Close Public Comment Period 2018-08 

Issue Final Decision 2018-12 

Begin Post-Decision Follow-up 2018 

Total (years) 6 

1

 The anticipated schedule will be revised as necessary (e.g., on any need arising under the Endocrine Disruptor Screening 

Program with respect to the active ingredients in this case). 

1.2 Updates to the Work Plan 

Since the publication of the PWP, the agency has made the following updates: 

 Added the following anticipated ecotoxicity data requirements for the degradate 

isocyanuric acid/cyanuric acid because of high uncertainty in the ECOSAR model 

results: 

o 850.1010 Aquatic invertebrates, acute, freshwater 

o 850.1025 or 850.1055 Estuarine/marine acute mollusk (shell deposition or 

embryo/larvae test) 

o 850.1075 Fish acute, freshwater (warm and cold water species) 

o 850.1075 Fish acute, estuarine/marine 

o 850.1300 Freshwater invertebrate life cycle 

o 850.1350 Estuarine/marine invertebrate life cycle 

o 850.1400 Fish early life-stage, freshwater or estuarine/marine species 

o 850.4100 Seedling emergence, Tier II – dose response, rice 

o 850.4150 Vegetative vigor, Tier II – dose response, rice 
Page 8 of 80

 Added the following anticipated fate data requirement for the isocyanuric acid/cyanuric 

acid to the table because it was omitted in error 

o 835.1230 or OECD 106 Batch Equilibrium 

 Added references. 

 Deleted references to dichloro-s-triazinetrione in Tables 3, 4, 5, and 7 throughout the 

document because the chemical is not included in this registration review. 

 Removed ingestion of treated drinking water from ORE scenarios (Table 10) because 

potential exposure from that route is addressed in section 3.2.2. 

 Updated Appendix C to address duplicate test results, and additional results found in the 

agency’s files 

 Added Appendix D to document the ECOSAR version 1.1. isocyanuric acid/cyanuric 

acid ecotoxicity modeling results 

 Corrected formatting and typographical errors 

 Added Appendix E to document public comments received and the agency’s responses. 

1.3 Case Overview 

The docket for the Chlorinate Isocyanurate Case (Case 0569) has been established at 

http://www.regulations.gov in docket number EPA-HQ-OPP-2012-0794. Except where 

otherwise noted, the three active ingredients [sodium dichloro-s-triazinetrione (PC Code: 

081404); trichloro-s-triazinetrione (PC Code: 081405); and sodium dichloro-s-triazinetrione 

dihydrate (PC Code: 081407)] in this case will be referred to collectively as “chlorinated 

isocyanurates.” Dechlorinated s-triazinetrione, also called cyanuric acid or isocyanuric acid 

(CAS Number 108-80-5), is a major degradate of these three chlorinated isocyanurates and has 

the PC Code 081402. Information on this degradate will be used in conducting both the human 

health and ecological risk assessment of the chlorinated isocyanurates, but there are no registered 

pesticide products containing dechlorinated-s-triazinetrione as the active ingredient, and 

therefore it is not considered as part of the case. 

There were products incorrectly identified in the PWP as dichloro-s-triazinetrione, which have 

since been reclassified as sodium dichloro-s-triazinetrione. Dichloro-s-triazinetrione (081401) is 

not being considered in this registration review. There are currently, no registered pesticide 

products containing dichloro-s-triazinetrione as an active ingredient. Although initially 

considered as part of the Chlorinated Isocyanurates case the only registration for potassium 

dichloro-s-triazinetrione (PC Code: 081403) was cancelled in 1993 and, therefore, will not be 

evaluated as part of this registration review. Although the penta-s-triazinetrione (PC Code: 

081406) was considered in the 1988 Registration Standard, it was not included in the 1992 

Reregistration Eligibility Document1

 and is not included in this registration review action since 

no registered products remain with the Agency. Therefore, the three active ingredients to be 

 

1

 Environmental Protection Agency, 1992. Reregistration Eligibility Document (RED) Chlorinated Isocyanurates 

http://www.epa.gov/pesticides/reregistration/REDs/old_reds/chlorinated_isocyanurates.pdf 
Page 9 of 80

assessed in Case 5069 are: sodium dichloro-s-triazinetrione (PC Code: 081404); trichloro-striazinetrione (PC Code: 081405); and sodium dichloro-s-triazinetrione dihydrate (PC Code: 

081407). 

The chlorinated isocyanurates and triazine herbicides share a symmetric triazine ring. However, 

the agronomic herbicides that are classified as s-triazine compounds have alkyl side chains. The 

chlorinated isocyanurates are not considered as part of the triazine cumulative assessment. 

As discussed in Appendix A, Environmental Fate, chlorinated isocyanurates are converted in the 

environment to the tautomer paired degradates, isocyanuric acid/cyanuric acid. The agency 

anticipates evaluating potential risk and hazards for chlorinated isocyanurates based on exposure 

to chlorine residual and on the paired tautomer degradates for human health and ecological 

effects. Risks from hypochlorous acid for cooling towers and water process system uses are 

discussed under the sodium and calcium hypochlorite case2

. 

1.4 Chemical Identification and Properties 

Table 3 presents the three active ingredients to be assessed in Case 5069: sodium dichloro-striazinetrione (PC Code: 081404); trichloro-s-triazinetrione (PC Code: 081405); and sodium 

dichloro-s-triazinetrione dihydrate (PC Code: 081407). All of these substances are substituted 

chlorinated salts or acids of isocyanuric acid ((CNOH)3) and act as chlorine releasers, they are 

hereinafter collectively referred to in this document as chlorinated isocyanurates. 

Table 3 - Chemical Identification Information for the Chlorinated Isocyanurates 

Chemical Name Sodium dichloro-striazinetrione Trichloro-s-triazinetrione Sodium dichloro-s-triazinetrione 

dihydrate 

Common Name Sodium 

dichloroisocyanurate Trichloroisocyanuric acid Sodium dichloroisocyanurate dihydrate 

Synonyms 

l,3-Dichloro-s-triazine-2,4,6 

(lH,3H,5H) trione sodium 

salt 

1,3,5-trichloro-s-triazine2,4,6 (lH,3H,5H) Trione 1,3-Dichloro-s-triazine-2,4,6 

(1H,3H,5H) trione sodium salt 

dihydrate 

Trade Names ACL 60; CDB 60; S.D.I.C. ACL 90 Plus; CDB 85; 

T.I.C.A.; TCCA. ACL 56; DICD 

PC Code 081404 081405 081407 

CAS Number 2893-78-9 87-90-1 51580-86-0 

Chemical Family Halogenated triazines 

Molecular 

Formula C3N3O3Cl2Na C3N3O3Cl3 NaC3N3O3Cl2·2H2O 

Molecular 

Weight 220.96 232.42 255.98 

Available 

chlorine % 

Theoretical 

Nominal 

60.0 - 64.48 89.5 - 91.5 55.0 % - 57.0 

 

2

 Na & Ca Hypochlorite Registration Review: Final Work Plan, Docket ID EPA-HQ-OPP-2012-0004-0006 
Page 10 of 80

Chemical Name Sodium dichloro-striazinetrione Trichloro-s-triazinetrione Sodium dichloro-s-triazinetrione 

dihydrate 

Molecular 

Structures: 

The chlorinated isocyanurates product chemistry relevant to risk assessment is presented in Table 

4 and details of the fate properties are discussed in Appendix A. 

Table 4 – Physical and Chemical Properties for the Chlorinated Isocyanurates

OPPTS Guideline Number/ 

Physical and Chemical 

Properties 

Sodium dichloro-striazinetrione Trichloro-striazinetrione Sodium dichloro-striazinetrione dihydrate 

830.1550 

Product identity and 

composition 

Refer to Table 3. Refer to Table 3. Refer to Table 3. 

830.6302/Color White White White 

830.6303/Physical State Granular 

Crystalline solid Crystalline solid Crystalline solid 

830.6304/Odor Chlorine Chlorine Chlorine 

830.6313 

Stability to sunlight, normal and 

elevated temperature, 

metals/metal ions 

Stable and relatively inert 

when dry 

Stable and relatively 

inert when dry 

Stable and relatively inert 

when dry 

830.6314 

Oxidation/Reduction: Strong oxidizing material Strong oxidizing material Strong oxidizing material 

830.7000/pH 6.1 (1 percent (%) 

solution) 2.9 (1% solution) 6.4 (1% solution) 

830.7200/Melting point 230-250 degrees Celsius 

(

 oC) (Decomposition) 

225-230 oC 

(Decomposition) 

240 oC 

(Decomposes) 

830.7200/Boiling point Not applicable (substances are all solids) 

830.7300 

Density 

35 pound per cubic foot 

(lb/cubic ft) 

850 – 950 kilogram per 

cubic meter (kg/cubic 

meter) 

Specific gravity 2.05 gram 

per milliliter (g/ml) at 20 o

C 

2.02 - 2.10 grams per 

cubic centimeter (g/cc) 62.56 lb/cubic ft. 

830.7550 

Partition coefficient 

 (n-octanol/water) 

-0.06 0.94 -0.06 
Page 11 of 80

OPPTS Guideline Number/ 

Physical and Chemical 

Properties 

Sodium dichloro-striazinetrione Trichloro-striazinetrione Sodium dichloro-striazinetrione dihydrate 

830.7840 

Solubility in water 24.8 g/100g at 26.8o

C 1.2 g/100g at 25 oC 26.2 g/l00 ml at 25°C 

830.7950 

Vapor pressure Very low, impossible to measure 

Source: From the 1988 Chlorinated Isocyanurates Registration Standard and 1992 Registration 

Eligibility Document (RED) 

1.5 Use/Usage Description 

1.5.1 Registrations 

There are 451 registered products that contain chlorinated isocyanurates. The distribution of 

products by specific isocyanurate is presented in Table 5. Most of the products are formulated as 

solid granules or tablets and a few products are formulated as liquids. 

Table 5 - Distribution of Products by Specific Chlorinated Isocyanurate 

Chemical Name PC Code Number of 

Products Percent a.i. Formulations 

Sodium dichloro-s-triazinetrione 081404 84 10 to 99b Granules, Tablets/Pellets, 

Impregnated Stick-On Patch 

Trichloro-s-triazinetrione 081405 246 1.9 to 100c

Granule, Tablets/Pellets, Water 

soluble packaging, soluble 

powder 

Sodium dichloro-s-triazinetrione 

dihydrate 081407 122 1.0 to 100 

Granules, Tablets/Pellets, Soluble 

Powder, Dust, Water soluble 

packaging 

N/A: not applicable 

a.i.: active ingredient 

a

 One product also contains trichloro-s-triazinetrione as an active at a declared content of 66.96% b

 Two products also contain trichloro-s-triazinetrione as an active: one with 44.6% and one with 70.54%. 

c

 Two products also contain sodium dichloro-s-triazinetrione as an active at declared content of 18.19 and 14.5% 

and one product also contains dichloro-s-triazinetrione as an active at a declared content of 53.2%. 

1.5.2 Summary of Registered Uses 

The chlorinated isocyanurates are registered for use as disinfectants, sanitizers, microbiocides, 

microbiostats, bacteriocides, bacteriostats, slimicides, algaecides, fungicides, fungistats, 

tuberculocides and virucides as summarized in Table 6. Application rates are provided in terms 

of the theoretical amount of available chlorine based on molecular weight ratios. For products 

that contain more than one chlorinated isocyanurate, the reported available chlorine application 

rate is expressed as the total chlorine produced from all chlorinated isocyanurates in the product. 
Page 12 of 80

Table 6 – Summary of Chlorinated Isocyanurate Antimicrobial Uses 

Use Site Application Rate 

(In Terms of Available Chlorine) 

Hard Surface Disinfection and Sanitization (Many Labels) 

Agriculture/Farm Structure and Equipment 100 to 971 parts per million (ppm) 

Animal Housing (poultry, swine, zoos and farms) 97 to 1,300 ppm 

Commercial, Institutional, Industrial Premise and Equipment 117 to 6,846 ppm 

Dairy Farm Milk Handling Facilities and Equipment 97 to 572 ppm 

Eating Establishments (Including Utensils) 100 to 150 ppm 

Egg Handling Equipment and Washing 97 to 300 ppm, 13,000 ppm 

Food Processing Plant Premise and Equipment 

(includes dairy/cheese, poultry, meat and seafood) 101 to 4,900 ppm 

Household/Domestic Dwellings (Includes floors) 100 to 4,720 ppm 

Laundry Premises and Equipment 113 to 457 ppm 

Medical/Veterinary Premise and Equipment 100 to 937 ppm 

Mushroom Houses 102 to 644 ppm 

Laundry Sanitizer, Deodorizer, and Destainer 

Laundry (Commercial, Industrial, Institutional) 60 to 200 ppm per load 

Oil Production (Many Labels) 

Secondary Oil Recovery Injection Water 0.5 to 10 ppm 

Oil Recovery Drilling Muds and Packer Fluids 0.5 to 10 ppm 

Water Treatment (Many Labels) 

Commercial and Industrial Cooling Water Systems 

(includes once through and recirculating cooling towers) 0.5 to 10 ppm 

Drinking Water (Emergency, public and individual systems)1 0.2 - 500 ppm 

Ornamental Ponds 0.5 to 20 ppm 

Pasteurizer Water Systems 0.5 to 10 ppm 

Sewage Treatment 0.2 to 3 ppm 

Swimming Pools and SPAs2 0.5 to 8 ppm 

Waterbed Water 16 ppm 

In-Can Material Preservative (Label #935-71 Only) 

Adhesives, Water Based 71 to 2,280 ppm 

Emulsions (Vinyl Acrylic, Acrylic and PVA) 71 to 2,280 ppm 

Joint Compounds 142 to 2,280 ppm 

Paints, Interior (Vinyl Acrylic, Acrylic and PVA) 285 to 1,140 ppm 

Pigment Dispersions 142 to 2,280 ppm 

Floriculture (Labels #72992-12 and #72992-16) 

Water Conditioner for Flower Cuttings (Tablet or Label) 17 to 78 ppm 

1

 Higher rates are for emergency treatments after floods. Maintenance rate is 0.2 ppm. 

2

 Higher rates are for shock and winterizing treatments. Water cannot be entered until level is below 4 ppm. 

Sodium dichloro-s-triazinetrione (PC Code: 081404), trichloro-s-triazinetrione (PC Code: 

081405), and sodium dichloro-s-triazinetrione dihydrate (PC Code: 081407) are all registered as 

disinfectants and sanitizers for use to control bacteria on indoor food and non-food contact hard 

surfaces and equipment at food processing plants, eating and food handling establishments, 

commercial and industrial premises, hospital and medical premises (human/veterinary), 

laboratories, zoos, livestock and animal living quarters, and indoor hard surfaces and contents of 

household/domestic dwelling premises. Additionally sodium dichloro-s-triazinetrione and 
Page 13 of 80

sodium dichloro-s-triazinetrione dihydrate are registered for use as a virucide on hard surfaces in 

hospitals (human/veterinary), institutional, and zoo premises, pet kennels, animal cages, zoo 

premises and animal enclosures and transport vehicles, animal feeding and water equipment, 

locker room premises, and shower and bathroom premises. These chlorinated isocyanurates are 

registered for use in residential, commercial, and institutional laundry products. 

Sodium dichloro-s-triazinetrione, trichloro-s-triazinetrione, and sodium dichloro-s-triazinetrione 

dihydrate, in addition to treating swimming pool water, are registered for use as microbiocides, 

microbiostats, bacteriocides, disinfectants, sanitizers, fungicides, and algaecides in non-food 

industrial water systems (air washer water systems, commercial/industrial water cooling systems, 

heat exchanger systems, cooling towers, lakes/ponds/reservoirs (without human or wildlife use), 

pasteurizer water, cannery cooling canal water, hot tub, whirl pool, and spa waters, ornamental 

ponds and lakes, aquaria water, ornamental fountains, sewage systems, waste water systems, 

sewage settling ponds, septic tanks, sewer lines (main), oil recovery drilling muds and packer 

fluids, and secondary oil recovery injection water. Additionally sodium dichloro-s-triazinetrione 

and sodium dichloro-s-triazinetrione dihydrate are registered for use as a virucide for the 

treatment of water used in spas, immersion ultrasonic tank water, whirlpool bath water, and shoe 

baths. Sodium dichloro-s-triazinetrione, trichloro-s-triazinetrione, and sodium dichloro-striazinetrione dihydrate are also registered for use as a virucide and bacteriocide for treatment of 

potable water. 

Formulation types include soluble concentrates both solid and flowable, wettable powder, water 

soluble packaging, granules, water dispersible granules, pellets, and tablets. There is a one 

product containing sodium dichloro-s-triazinetrione registered only for use of impregnated 

patches for placement on fresh cut flowers as a bactericide for slime-forming bacteria. 

The labels indicate that the chloroisocyanurates can be applied to industrial water treatment 

systems and materials being preserved using both open pour and closed systems, applied to 

swimming pools and spas using open pour systems, applied to various hard surfaces using 

sprayers, foamers, mops and wipes, and applied to food processing equipment and systems using 

immersion and circulate in place methods. Some labels, such as EPA Reg. Nos.1677-91 and 

66570-2, also indicate that fogging can be used for applications in dairy, beverage and food 

processing plants. 

1.5.3 Usage Information 

According to the Kline Biocides Report for 2004/2005 (Kline, 2006), the estimated U.S. 

consumption of chloroisocyanurates for 2004 was 195 million pounds. This consumption was 

distributed among recreational water (188.5 million pounds), cooling water (5.2 million pounds) 

and household, industrial and institutional disinfectants and sanitizers (1.1 million pounds). 

According to a more recent report (Chemical Economics Report, 2012), “The global market for 

chlorinated isocyanurates is forecast to grow at an average annual rate of almost 3.5%”.
Page 14 of 80

1.6 Regulatory History 

The chlorinated isocyanurates were first registered in the United States in 1958 for use as 

disinfectants, sanitizers, algicides, and fungicides. Sodium dichloro-s-triazinetrione was first 

registered in the United States in 1968; trichloro-s-triazinetrione was first registered in the 

United States in 1959; and sodium dichloroisocyanurate dihydrate was initially registered as a 

sanitizer in the United States on March 17 1964. The Agency completed a reregistration 

eligibility decision document (RED) in 1992, which included a reregistration decision on all 

current uses except the material preservative uses, and all of the existing uses at that time were 

found to be eligible for registration. The post-RED data call-in (DCI) was issued in May 1993. 

1.6.1 Recent/Pending Regulatory Actions 

There is currently one pending registration for sodium dichloro-s-triazinetrione, one pending 

registration for trichloro-s-triazinetrione and one for sodium dichloro-s-triazinetrione dihydrate. 

1.6.2 Tolerance Information 

A tolerance exemption has been established for sodium dichloroisocyanurate used as a sanitizer 

on food contact surfaces of public eating places, dairy processing equipment, and food 

processing equipment and utensils [40 CFR 180.940(a)]. Tolerance exemptions have also been 

established for trichloroisocyanuric acid and dichloroisocyanuric acid and its sodium and 

potassium salts used as sanitizers on food contact surfaces of food processing equipment and 

utensils [40 CFR 180.940(c)]. All these sanitizers must be used such that the final use 

concentration of di- and trichloroisocyanuric acid chemicals does not exceed 100 ppm 

determined as total available chlorine. The Agency intends to add sodium dichloroisocyanurate 

dihydrate (51580-86-0) to the exemption in 40 CFR 180.940(c). 

1.7 Incidents 

1.7.1 Human Health 

A total of approximately 6,500 human health incidents are listed in the Office of Pesticide 

Programs (OPP) Incident System for the chlorinated isocyanurates for the years 1992 to the 

present. A summary of these incidents is given in Table 7. The severity of the incidents range 

from minor effects such as transient respiratory irritation represented by code HD (Human 

Minor) to severe effects such as injuries and death represented by codes HB (Human Major) and 

HA (Human Fatality). 

Approximately 4,900 of the incidents involved the swimming pool uses. The most severe 

incidents were caused by label misuses such as premixing the chloroisocyanurate pool products 

with small amounts of water or incompatible chemicals such as bleach. These two actions 

caused explosions and the release of chlorine gas resulting in injuries such as chemical burns and 

pulmonary edema. The labels clearly state that chloroisocyanurates should not be handled in this 

manner. Less severe incidents have occurred when people have been exposed to irritating 
Page 15 of 80

“fumes” when opening containers or when products fell out of floating dispensing containers 

(i.e., floaters) causing excessive dosing of the pool. 

Approximately 680 incidents are associated with the food processing uses where 

chloroisocyanurate is used to treat beverage or milkshake machines. Two major (HB) incidents 

occurred when a person drank what he or she believed to be ice tea from an unlabeled container 

containing chloroisocyanurate sanitizer solution and when a person drank a milkshake from a 

milkshake machine that had not been properly rinsed following treatment with 

chloroisocyanurate. 

Another 750 minor (HD) incidents are associated with the toilet bowl cleaning and hard 

surface disinfection uses and 7 minor incidents are associated with the industrial uses. 

Table 7 - Incidents Reported for the Chlorinated Isocyanurates 

Product Type Number of Incidents1

HA HB HC HD HE 

Sodium dichloroisocyanurate (081404) 

Food Processing 0 0 0 1 0 

Industrial Uses – Cooling Water, Paper Mills, Material Preservation 0 0 0 3 0 

Pools and Spas 0 9 1 1014 26 

Miscellaneous and Unspecified 0 0 0 8 0 

Trichloro-isocyanuric Acid (081405) 

Toilet Bowl 0 0 0 78 0 

Industrial Uses – Cooling Water, Paper Mills, Material Preservation 0 0 0 2 1 

Pools and Spas 3 19 0 3425 49 

Miscellaneous and Unspecified2 0 0 0 19 3 

Sodium dichloro-isocyanurate dihydrate (081407) 

Food Processing 0 2 0 675 2 

Hard Surface Disinfection 1 0 0 671 80 

Industrial Uses – Cooling Water, Paper Mills, Material Preservation 0 0 0 4 0 

Pools and Spas 1 4 0 402 26 

Miscellaneous and Unspecified 0 1 0 0 0 

1

 HA = Human Fatality, HB = Human Major, HC = Human Moderate, HD = Human Minor, HE = Human Unspecified 2

 Two of the HD incidents involved the misuse of an industrial product in a swimming pool. 

1.7.2 Ecological 

No chlorinated isocyanurate ecological incidents have been reported in the Agency’s OPP 

Incident Data System (IDS). 

2 Anticipated Data Needs 

Table 8 presents a summary of the data anticipated as being needed to support this registration 

review. 
Page 16 of 80

Table 8 - Studies Anticipated as Needed for the Registration Review of the Chlorinated 

Isocyanurates 

OCSPP GLN Study Name Test 

Substance

Time 

Frame 

(Months 

from 

DCI 

Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) 

Triggering Data 

Requirement

Applicable Exposure 

Scenarios

875.1300 Indoor Exposure, 

Inhalation 

Degradate 

(isocyanuric 

acid) 

24 

Occupational and 

Residential 

Handler 

All See notes 1, 2, 3 and 4. 

875.1700 Product Use 

Information TGAI 12 All All All above scenarios. 

875.2300 Indoor Surface 

Residue Dissipation TGAI 24 Residential Household floors5

 Toddlers playing on 

disinfected floors 

850.1010 Aquatic invertebrates, 

acute, freshwater 

Degradate 

(isocyanuric 

acid) 

24 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1025 or 

850.1055 

Estuarine/marine acute 

mollusk (shell 

deposition or 

embryo/larvae test) 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1075 

Fish acute, freshwater 

(warm and cold water 

species7

) 

Degradate 

(isocyanuric 

acid) 

18 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1075 Fish acute, 

estuarine/marine 

Degradate 

(isocyanuric 

acid) 

18 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1300 Freshwater 

invertebrate life cycle 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.1350 Estuarine/marine 

invertebrate life cycle 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.14008

Fish early life-stage, 

freshwater or 

estuarine/marine 

species 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.41009

Seedling emergence, 

Tier II – dose 

response, rice 

Degradate 

(isocyanuric 

acid) 

12 Aquatic/Terrestrial 

exposure and risk 

All6 except in-can 

material preservatives 

and floriculture patch 

Transport to the aquatic 

environment 

850.41509 Vegetative vigor, Tier 

II – dose response, rice 

Degradate 

(isocyanuric 

acid) 

12 

Aquatic/Terrestrial 

organism exposure 

and risk 

All6

 except in-can 

material preservatives 

and floriculture patch 

Transport to the aquatic 

environment 

850.440010 

Aquatic Plant Testing 

using Lemna sp., Tier 

II 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.450011 

Algal Toxicity Tier II 

–marine diatom, 

freshwater diatom, 

green algae 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 

850.455011 Algal Toxicity Tier II - 

Cyanobacteria 

Degradate 

(isocyanuric 

acid) 

12 Aquatic organisms All6 Transport to the aquatic 

environment 
Page 17 of 80

OCSPP GLN Study Name Test 

Substance

Time 

Frame 

(Months 

from 

DCI 

Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) 

Triggering Data 

Requirement

Applicable Exposure 

Scenarios

835.1230 (or 

OECD 106) Batch Equilibrium 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6 Transport and fate to the 

aquatic environment 

835.311012 Ready 

Biodegradability 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

835.322012 Porous Pot Test 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

835.324012 

Simulation Test – 

Aerobic Sewage 

Treatment: A. 

Activated Sludge Units 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

835.328012 

Simulation Test to 

Assess the 

Biodegradability of 

Chemicals Discharged 

to wastewater 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

835.4300 Aerobic aquatic 

metabolism 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6 Transport to the aquatic environment 

835.4400 Anaerobic aquatic 

metabolism 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6 Transport to the aquatic 

environment 

OECD 209 or 

850.330013 

Activated Sludge 

Respiration Inhibition 

(ASRI) 

Degradate 

(isocyanuric 

acid) 

12 Aquatic exposure 

and risk All6

Transport to wastewater 

treatment plant and 

aquatic environment 

860.146014 Food-handling TEP 24 Dietary and 

aggregate risk 

Food processing, 

dairy, and public 

eating establishments 

Dietary 

Special Study15 Migration studies TEP 24 Dietary and 

aggregate risk 

Adhesives and 

pulp/paper mill 

slimicide use 

Dietary 

OCSPP: Office of Chemical Safety and Pollution Prevention; GLN: guideline number, DCI: data call-in 

1 Applicable Occupational Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for hard surface 

disinfection and pool treatment; 2- Open pour granules for material preservation; 3- Mop, wipe and trigger spray for 

hard surface disinfection; 4- Hand wand spray disinfection of egg and food processing plants; 5- Fogging 

disinfection of egg and food processing plants; and 6- Brush, roller and spray application of preserved paints. 

2 Applicable Residential Handler Exposure Scenarios: 1- Open pour liquids, granules and powder for pool treatment; 

2- Mop, wipe and trigger spray for hard surface disinfection; and 3- Brush, roller and spray application of preserved 

paints. 

3 It may be possible to use proprietary surrogate exposure data if data compensation issues can be addressed. 

4 If the labels are modified to require automatic foggers in place of hand held foggers, then the study of hand held 

fogging exposures would not be expected to be needed. 

5 If surface residue data are not available, then the standard assumption of 100 percent transferable surface residue 

will be used which might overestimate the risk. For Hard Surface Flooring, only. 
Page 18 of 80

6

 Industrial Process and Water Treatment: Cooling Tower and Swimming Pools and Water Beds; Hard Surfaces 

Disinfectants and Sanitizers: Down-the-Drain (DtD) residential and industrial; Laundry Products: DtD residential 

and commercial; Material Preservatives: DtD Production and In-Service. 

7 Except for the industrial processes and water system uses, testing of a second freshwater species (cold or warm 

water) may be waived if isocyanuric acid is not stable and the median lethal concentration (LC50) in the first species 

tested is >1 ppm. 

8 Expected to be required for the more acutely sensitive of the freshwater and estuarine/marine fish species tested. 

9 Data may be waived for uses where environmental exposure concentrations will be less than the aquatic plant 

growth Tier II (850.4400, 850.4500, and 850.4550) no observable adverse effect concentration (NOAEC) values. 

10 Except for industrial process and water treatment uses, a use may be eligible for data waiver if the aquatic plant 

NOAEC results are all greater than or equal to 1 ppm. 

11 All uses footnoted with marine diatom and freshwater diatom data for material preservative uses, hard surface 

disinfection and sanitization uses, and floriculture use may be eligible for data waiver if green algae (Selenastrum 

capricornutum) NOAEC results are greater than or equal to 1 ppm. The anticipated DCI will address this. 

12 EPA has published final guidelines for four biodegradation studies. The biodegradation study anticipated to be 

required for chlorinated isocyanurates is for the degradate (Isocyanuric acid based on an Activated Sludge 

Respiration Inhibition Test). 

13 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine 

which of these four biodegradation tests would be anticipated to be required. If the ASRI test EC50 is less than or 

equal to 20 milligrams per liter (mg/L), then either the (i)Biodegradation in Activated Sludge Study or (ii) 

Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test would be 

anticipated to be required. If the ASRI test EC50 is greater than 20 mg/L, then the DCI expected to be issued would 

provide that the registrant would choose to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in 

Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous 

Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to 

be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in 

Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous 

Pot study would be expected to be required. The appropriate Test Substance to satisfy the guideline requirement is 

the degradate (isocyanuric acid). 

14 Residue chemistry data are anticipated to be needed to determine dietary exposure to cyanuric acid/isocyanuric 

acid following sanitization of food contact surfaces of food processing plants (including dairies) and food-handling 

facilities (including public eating places). Protocol submission is recommended. The anticipated DCI will address 

this. 

15 Migration of cyanuric acid/isocyanuric acid from preserved adhesive to food and from paper/paperboard to food 

following the slimicide use. The anticipated DCI will provide that a protocol must be submitted for EPA approval 

prior to initiating the study. 
Page 19 of 80

3 Human Health Risk Assessment 

The Agency anticipates the need to conduct a human health risk assessment for the chlorinated 

isocyanurates. The Agency expects to require additional data for use in conducting the 

registration review. 

3.1 Existing Toxicological Endpoints 

EPA anticipates the need to revise the existing toxicological endpoints as part of this registration 

review. Table 9 presents the existing toxicological points of departure (POD) for the chlorinated 

isocyanurates. The existing PODs were established by the EPA Hazard Identification 

Assessment Review Committee (HIARC) in 2001 based on the toxicity database for the 

isocyanuric acids. It should be noted that the PODs for dermal exposure are based on oral 

studies and are used with a dermal absorption factor of 1 percent to account for route to route 

extrapolation. Because the PODs for dermal exposure are the oral NOAELs of 200 milligrams 

per kilogram per day (mg/kg/day) and 154 mg/kg/day and the dermal absorption is 1 percent, the 

dermal equivalent PODs are 20,000 mg/kg/day and 15,400 mg/kg/day. Because these PODs are 

much higher than the limit dose of 1000 mg/kg/day for dermal toxicity studies, the dermal 

toxicity is very low and does not need to be assessed. See Appendix B for additional information. 

Table 9 – Existing Toxicology Endpoints 

Exposure 

Scenario 

Dose 

(mg/kg/day) Point of Departure (POD) Study (MRID) 

Acute Dietary 

(females 13+) 

NOAEL= 200 

mg/kg/dayA

UF = 100 

Increased incidence of hydrocephaly at 500 

mg/kg/day. 

Developmental 

Toxicity – Rabbit 

(42054101) 

Acute RfD =2.0 mg/kg/day 

Acute Dietary 

(general 

Population) 

N/A No appropriate endpoint was identified for the general population 

Chronic Dietary 

NOAEL =154 

mg/kg/dayA

UF = 100 

Decreased survival in male rats and lesions of the 

urinary tract and heart at the next highest dose of 

502 mg/kg/day.

Chronic Toxicity / 

Carcinogenicity- Rat 

(00126362) 

Chronic RfD = 1.5 mg/kg/day 

Incidental Oral, 

Short-Term N/A No appropriate POD was identified for short-term incidental oral risk. 

Incidental Oral, 

Intermediate-term 

NOAEL = 204 

mg/kg/dayA

Based upon hyperplasia of the urinary bladder at a 

dose of 672 mg/kg/day. 

90-Day Oral Toxicity 

– Rat 

(00063477) 

Short- and 

Intermediate-Term 

(Dermal) 

NOAEL= 200 

mg/kg/dayA,B

UF = 100C

Increased incidence of hydrocephaly at 500 

mg/kg/day. 

Developmental 

Toxicity – Rabbit 

(42054101) 
Page 20 of 80

Exposure 

Scenario 

Dose 

(mg/kg/day) Point of Departure (POD) Study (MRID) 

Long-Term 

(Dermal) 

NOAEL=154 

mg/kg/dayA,B 

UF = 100C

Decreased survival in male rats and lesions of the 

urinary tract and heart at the next highest dose of 

502 mg/kg/day.

Chronic Toxicity/ 

Carcinogenicity –Rat 

(00126362) 

Inhalation(Any 

time point) 

NOAEL= 

0.0032 mg/LD

UF = 100C

Based on increased incidence of clinical signs, 

decreased body weight, and increased relative lung 

weight at the next highest dose level. 

28-Day Inhalation 

Toxicity – Rat 

(00132438) 

Abbreviations: MRID = Master Record Identification; UF = Uncertainty factor, NOAEL = No Observed Adverse Effect Level, 

RfD = Reference Dose 

A These PODs are based on toxicity studies of isocyanuric acid as discussed in the HIARC report of 1/25/2001. 

B

 Since an oral POD was selected for dermal risk assessments, a dermal absorption value of 1.0 percent (i.e. a 

dermal absorption factor of 0.01) should be used in route-to-route extrapolations. This value is based on available 

data as discussed in an OPP Memorandum of 20 March 1980 from Robert Zendzian, Ph. D. to James Skaptason. 

C

 The HIARC report lists uncertainty factors (UF) of 100 for occupational dermal and inhalation exposure. The 

HIARC report does not list UFs for residential exposure. 

D. This NOAEL is from a study where the test substance was sodium dichloro-s-triazinetrione. 

3.2 Dietary Exposure 

The Agency anticipates the need to conduct a dietary assessment. Uses of chlorinated 

isocyanurates that may result in dietary exposures include food processing plants including 

dairies and food-handling facilities including public eating places, emergency drinking water, 

and individual and public drinking water systems including tanks, wells, reservoirs, and basins. 

Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which reflects the 

reference dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA 

Safety Factor (SF). This calculation is performed for each population subgroup for which an 

endpoint exists. A risk estimate that is less than 100% of the acute or chronic PAD is not of 

concern. Acute dietary risk for Chlorinated Isocyanurates will be assessed by comparing dietary 

exposure estimates expressed in mg/kg/day to the acute Population Adjusted Dose (aPAD) and 

chronic Population Adjusted Dose (cPAD). 

3.2.1 Food 

Human dietary exposure to chlorinated isocyanurate residues may occur as a result of their use to 

sanitize food contact surfaces of food processing plants including dairies and food-handling 

facilities including public eating places. After treatment, most product labels state that food 

contact surfaces should be drained and that they should not receive a potable water rinse prior to 

reuse. However, some product labels state that a potable water rinse should be made after 

treatment. This issue will be addressed during the risk assessment stage of this registration 

review. Chlorinated isocyanurates are also used to preserve adhesives and as slimicides during 

production of paper/paperboard which may be used for food-contact purposes (labels are silent 

re: whether food contact is prohibited). 
Page 21 of 80

The Agency did not conduct a dietary risk assessment to support the 1992 RED for the 

Chlorinated Isocyanurates because, at that time, the uses noted above were under the purview of 

the Food and Drug Administration. Also, FQPA had not yet become law meaning that aggregate 

risk assessments were not conducted. Residue chemistry data are expected to be needed to 

determine dietary exposure to the stable, tautomeric degradate pair of cyanuric acid and 

isocyanuric acid following sanitization of food contact surfaces of food processing plants 

(including dairies) and food-handling facilities (including public eating places), adhesive 

preservation, and slimicide use in the pulp slurry to make paper/paperboard for food contact. 

The acute and chronic assessments to be conducted during registration review will estimate 

dietary exposure to chlorinated isocyanurates and the degradate cyanurate/isocyanurate for all 

population subgroups. 

3.2.2 Drinking Water 

The chlorinated isocyanurates are registered for emergency drinking water treatment as well as 

routine (non-emergency) treatment of individual and public drinking water systems including 

tanks, wells, reservoirs, and basins. While the chlorinated isocyanurate active ingredients are not 

persistent, contamination of drinking water by the degradate cyanurate/isocyanurate may occur 

as a result of discharge of waste water from paper and paperboard mills, down-the-drain from 

swimming pools or food-handling establishments, or run-off from livestock premises. 

Chlorinated isocyanurates degrade rapidly to cyanurate/isocyanurate and hypochlorous acid. 

Both parent compounds and cyanurate/isocyanurate are highly water-soluble and weakly sorbed 

to soil, sediment, and sludge. The routine water treatment use was assessed in response to a 

registrant proposal that EPA approve these uses on four of their product labels (T. McMahon, 

3/26/01, D270655). Estimated exposures were compared to the cPAD value of 1.5 mg/kg/day as 

determined by the HIARC (report dated 1/25/01). Chronic dietary risks were reported to be 2% 

of the cPAD for adults and 6% of the cPAD for children. 

The acute and chronic assessments to be conducted during registration review will estimate 

drinking water exposure to the degradate cyanurate/isocyanurate for all population subgroups. 

3.3 Occupational and Residential (ORE) Exposures 

3.3.1 ORE Exposure Assessed in the RED 

Occupational and Residential (ORE) Exposures were not assessed in the RED because “the 

chlorinated isocyanurates did not appear to induce significant acute (except eye irritation), 

subchronic or chronic toxicity based on available information”. The RED further stated that “the 

toxicity data indicate that these compounds do not meet the Agency's toxicity criteria for the 

requirement of post-application re-entry and/or mixer/loader/applicator exposure monitoring 

data. Accordingly, occupational and residential exposure data are not required to support the 

reregistration of the chlorinated isocyanurates.” 
Page 22 of 80

3.3.2 ORE Exposures Assessed after the RED 

The dermal and incidental oral exposures of persons swimming in pools treated with chlorinated 

isocyanurates were assessed in D270656 of 2/26/2001 using the endpoints established by the 

HIARC. These endpoints included the intermediate term incidental oral NOAEL of 204 

mg/kg/day and the long term NOAEL of 154 mg/kg/day. These exposures were calculated for 

both adult (77 kg) and child (29 kg) competitive swimmers using the SWIMODEL and assuming 

an isocyanuric acid concentration of 55 mg/liter, an exposure time of 3.0 hours per event, an 

event frequency of 150 events per year, a water ingestion rate of 0.05 liters per hour and a 

permeability coefficient of 1.5 x 10-5 cm/hr. The oral MOEs were 270 for adults and 240 for 

children and the dermal MOEs were 720 for adults and 270 for children. The combined MOEs 

were 160 for adults and 110 for children. All these MOEs were considered to be not of concern 

because they exceeded the target MOE of 100. 

The exposures to persons swimming in public pools treated with chlorinated isocyanurates are 

also measured using biomonitoring of urine to determine water ingestion rates in a study 

conducted by the EPA Office of Research and Development (ORD). Approximately 550 

swimmers were included in this study and the pilot results from 53 swimmers were reported in 

Dufour, 2006 and incorporated into the Exposure Factors Handbook (EPA, 2011). 

3.3.3 ORE Exposures that will Need to Be Assessed for Registration Review 

Because endpoints of concern were identified after the RED for incidental oral and inhalation 

exposures, occupational and residential exposures will need to be assessed for registration 

review. Although endpoints were also selected for dermal exposure, dermal exposures will not 

need to be assessed for reasons previously discussed in Section 3.1. A listing of the exposure 

scenarios that need to be assessed is included in Table 10. 

Table 10 - ORE Scenarios for the Chlorinated Isocyanurates 

Scenario Exposure 

Route(s) Duration 

Occupational Exposures

Open pour granules and powder for hard surface 

disinfection and pool treatment Inhalation Short and Intermediate Term 

Open pour granules for material preservation Inhalation Short and Intermediate Term 

Mop, wipe and trigger spray application for disinfection 

(Medical and CII premise and equipment) Inhalation Short and Intermediate Term 

Hand wand spray application for disinfection 

(animal housing, food processing plants) Inhalation Short and Intermediate Term 

Fog application for disinfection 

(egg and food processing plants) Inhalation Short and Intermediate Term 

Brush, Roller and Spray Application of Preserved Paint Inhalation Short and Intermediate Term 

Residential Exposures

Mop, wipe and trigger spray application for disinfection 

(Household/domestic dwellings, includes floors) Inhalation Short and Intermediate Term 

Open and pour granules and powder for pool treatment Inhalation Short Term 
Page 23 of 80

Brush and Roller Application of Preserved Paint Inhalation Short Term 

Swimming in Treated Pools Incidental oral Short and Intermediate Term

Toddlers playing on disinfected floors Incidental Oral Short and Intermediate Term

3.4 Aggregate and Cumulative Exposure 

3.4.1 Aggregate Exposures 

Upon a reevaluation and selection of toxicological endpoints, combined with the human health 

exposure assessments expected as a part of this registration review case, aggregate exposures 

will need to be assessed. This assessment will likely include dietary exposures and residential 

exposures. 

3.4.2 Cumulative Exposures 

With respect to cumulative exposure, unlike other pesticides for which EPA has followed a 

cumulative risk approach based on a common mechanism of toxicity, EPA has not made a 

common mechanism of toxicity finding as to the chlorinated isocyanurates and any other 

substances and the chlorinated isocyanurates do not appear to produce a toxic metabolite 

produced by other substances. For the purposes of this registration review, therefore, EPA has 

not assumed that the chlorinated isocyanurates have a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs at 

http://www.epa.gov/pesticides/cumulative/. 

4 Environmental Risk Assessment 

The Agency has not conducted a risk assessment that supports a complete endangered species 

determination for the chlorinated isocyanurates. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether the use of chlorinated 

isocyanurates has 'no effect' or 'may affect' federally listed threatened or endangered species 

(listed species) or their designated critical habitats. When an assessment concludes that a 

pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will 

consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the 

Services), as appropriate. 

4.1 Environmental Conceptual Model Exposure Pathways 

Based on the chemical/physical properties and environmental fate studies (Appendix A) and the 

uses in Table 6, the Agency has developed conceptual models for the environmental exposure to 

the chlorinated isocyanurates and their major metabolites/degradates. For all uses, the Agency 

assumes that environmental exposures may occur, especially from the cyanuric/isocyanuric acid 

metabolites, but bioconcentration will not be significant because of their low log Kow (log P) 

and high water solubility values. This environmental exposure is expected to be of shorter 

duration in the presence of acclimated microorganisms or anaerobic conditions, based on 
Page 24 of 80

literature references (Zeyer et al., 1980, Ernst and Rehm, 1990, Jessee et al., 1983, Cook et al., 

1985, Saldick et al., 1974). The ultimate breakdown products of cyanuric acid are carbon 

dioxide (CO2) and ammonia (NH3), both of which can be released into air or incorporated into 

microbial biomass. Figure 1 below contains the conceptual model for the use of disinfection and 

sanitizing products including cleaning products for floors and laundry additives (e.g., pre-wash 

cycle sanitizers, cleansers) which go down the drain after use. Figure 2 below contains the 

conceptual model for swimming pools and waterbed water uses. Figure 3 contains the 

conceptual model for cooling towers. Figure 4 contains the conceptual model for in-can 

preservatives. 

The use of chlorinated isocyanurates in industrial processes and water systems has a potential to 

expose aquatic organisms to hypochlorous acid and cyanuric/isocyanuric acid. However, 

hypochlorous acid has a finding of “no effect” for cooling towers and water process system uses 

and therefore is not of concern for chlorinated isocyanurates3. The risk assessment to be 

conducted as part of this registration review will evaluate risk from the chlorinated isocyanuric 

acid metabolite, isocyanuric acid. 

 

3

 Na & Ca Hypochlorite Registration Review: Final Work Plan, Docket ID EPA-HQ-OPP-2012-0004-0006 
Page 25 of 80

Figure 1 Conceptual Model for Ecological Exposure and Effects of Chlorinated 

Isocyanurates and their Reaction Products/Degradates from Sanitizing and Disinfecting 

Uses for Laundry and Hard Surfaces to Aquatic and Terrestrial Organisms 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs

related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Surface Water/Sediment

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell,

roots, leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Disinfection and Sanitizing Products: cleaning products for floors  and

laundry additives (e.g., pre‐wash cycle sanitizers, cleansers)

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Down‐the‐drain disposal
Page 26 of 80

Figure 2 Conceptual Model for Ecological Exposure and Effects of Chlorinated 

Isocyanurates and their Reaction Products/Degradates from Swimming Pool and Water 

Bed Uses to Aquatic and Terrestrial Organisms 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEsrelated

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEsrelated to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptakeor sorption/cell,

roots, leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here thistermrefersto animals (terrestrialor aquatic)that eat notjustfish but any aquatic animal (e.g., amphibians,mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Mostlikely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Pool Treatment and Waterbed Use

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Disposal of Water to

sanitary drain system

Stormwater drain disposal

SurfaceWater/Sediment
Page 27 of 80

Figure 3 Conceptual Model for Ecological Exposure and Effects of Chlorinated 

Isocyanurates and their Reaction/Degradates from Cooling Water Tower Uses to Aquatic 

and Terrestrial Organisms 

 

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Surface Water/Sediment

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell, roots,

leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

Cooling Tower (Once Through and Recirculating)

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Direct Discharge
Page 28 of 80

Figure 4 Conceptual Model for Ecological Exposure and Effects of Chlorinated 

Isocyanurates and their Reaction/Degradates from the Use and Disposal of In-Can or InContainer Material Preservatives to Aquatic Organisms 

4.2 Ecological Effects Assessment 

Ecological effects data are used as measures of direct and indirect effects to biological receptors. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with the 

available open literature obtained from ECOTOX will be used to evaluate the potential direct and 

indirect effects of the chlorinated isocyanurates and their degradates to aquatic and terrestrial 

receptors. Data discussed herein are from registrant-submitted data and from the EPA Office of 

Water’s Ambient Water Quality Criteria for Chlorine - 1984 (EPA 1985). 

4.2.1 Mechanism of Action 

In the aquatic environment, toxic action of chlorinated isocyanurates is largely due to the 

formation of hypochlorous acid when chlorine reacts with water. Adverse effects of 

hypochlorous acid are due mainly to its corrosive action. Acute necrosis may occur. Fish gillsStressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption by

cells, roots, leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals(terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

In‐Surface Use of In‐Can or In‐Container Material Preservatives

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

Down‐the‐drain disposal of waste water from

paint roller, brush, and tray rinsate

Surface Water/ Sediment

Leaching from Exterior Facades

and Structures to Storm Drains
Page 29 of 80

structure may be damaged; gill necrosis can lead to respiratory problems and asphyxiation. The 

protective slime coating on fish also may be removed due to corrosive action. 

4.2.2 Measures of Effect (Ecotoxicology Endpoints)

Current selected ecotoxicological endpoints for conducting the risk assessment are provided in 

Table 11. All available ecotoxicity endpoints from studies submitted by registrants are tabulated 

separately for each isocyanurate in Appendix C. Available information on water quality criteria 

for chlorine residual is also discussed in Appendix C. The Ambient Water Quality criteria for 

Chlorine – 1984 document contains a review of public literature on effects of chlorine (total 

residual chlorine (TRC) for freshwater species and chlorine produced oxidants (CPO) for 

estuarine/marine species) and derives freshwater and saltwater organism acute and chronic water 

quality criteria. Current ambient water quality criteria (EPA, 2012) for chlorine are based on the 

1986 Water Quality Document (EPA, 1986) which contained slight data updates to the 1984 

document. OPP uses the most sensitive toxicity values for assessing risk to each receptor group. 

The endpoints that are expected to be used for the chlorinated isocyanurates ecological risk 

assessment are presented in Table 11. Data gaps also are indicated. No effects data on 

cyanurate/isocyanuric acid have been submitted to the OPP for review in support of pesticide 

registration. The Agency recognizes that isocyanuric acid is an EPA high production volume4

(HPV) chemical for which a Screening Information Data Set (SIDS) Assessment Report was 

performed (OECD SIDS 1999 and IIAHC 2003). Values found in these sources have been listed 

in Appendix C and consist of freshwater fish and invertebrate and green algae data. While some 

critical elements of these studies are identified in the HPV SIDS files, there is insufficient 

information available on the studies for AD to review the studies for purposes of a risk 

assessment. ECOSAR v1.1 was used to estimate freshwater and estuarine/marine fish and 

invertebrate acute and chronic values and the median effect concentration (EC50) and maximum 

allowable toxicant concentration (MATC; geometric mean of the NOAEC and LOAEC) for 

green algae. 

Table 11 – Existing Ecological Effects Endpoints 

Receptor 

Group 

Test 

Materiala Surrogate 

Species 

Risk 

Scenario Toxicity Endpoint Reference 

Freshwater fish 

TRC Rainbow trout Acute 96-h LC50 = 80 μg ai/L MRID 00150966

Chronic AWQ criteria = 11 ug/l EPA 2012b

isocyanuric 

acid 

Generic Acute 96-h LC50 = 72.0 mg/L ECOSAR v 1.1 

Rainbow trout Chronic MATC = 1.85 mg/L ECOSAR v1.1 

Freshwater 

invertebrates 

TRC Waterflea Acute 48-h EC50 = 110 μg/L MRID 255593 

Chronic AWQ criteria = 11 ug/L EPA 2012b

isocyanuric 

acid Waterflea Acute 48-h EC50 = 34.65 mg/L ECOSAR v1.1 

Chronic NOEC = 1.49 mg/L ECOSAR v 1.1 

Estuarine/marine 

fish 

CPO Atlantic 

silverside 

Acute LC50 = 37 μg/L EPA 1985 

Chronic AWQ criteria = 7.5 ug/L EPA 2012b

Isocyanuric Generic fish Acute 96-h LC50 = 46.9 mg/L ECOSAR v1.1 

 

4

 http://www.epa.gov/hpv/pubs/general/hpvchemdata.htm 
Page 30 of 80

Receptor 

Group 

Test 

Materiala Surrogate 

Species 

Risk 

Scenario Toxicity Endpoint Reference 

acid Chronic MATC = 2.46 mg/L ECOSAR v1.1 

Estuarine/marine 

invertebrates 

CPO Eastern oyster Acute EC50 = 26 μg/L EPA 1985 

Chronic AWQ criteria = 7.5 ug/Lc EPA 2012b

Isocyanuric 

acid Mysid Acute 96-h LC50 = 6.97 mg/L ECOSAR v1.1 

Chronic MATC = 4.82 mg/L ECOSAR v1.1 

Algae 

TRC 4 spp. EC50 Not required 

NOAEL Not required 

isocyanuric 

acid Green algae EC50 96-h EC50 = 0.114 mg/Lb

 ECOSAR v1.1 

NOAEL MATC = 0.057 mg/Lb ECOSAR v1.1 

Aquatic vascular 

plants 

TRC 

Lemna 

EC50 Not required NOAEL 

Isocyanuric 

acid 

EC50 Data required NOAEL 

Birds Trichloro-striazinetrione Mallard Acute LD50 = 1021 mg ai/kg-bw MRID 00126521

Chronic Not required 

Mammals 

Chlorinated 

isocyanurates Lab. rat Acute LD50 = 787 mg/kg-bw MRID 00150959

Chronic >1000 mg/kg-bw/day See Section 4.1.3

isocyanuric 

acid Lab. rat Acute LD50 = 7700 mg/kg-bw OECD SIDS 1999

Nontarget insects Isocyanuric 

acid Honey bee Acute Not required 

a

 TRC (total residual chlorine) refers to the sum of free chlorine and combined chlorine in fresh water; in saltwater, 

in which chlorine forms will react with bromide, CPO (chlorine-produced oxidants) refers to the sum of the 

oxidative products. 

b

 Office of Water Aquatic Water Criteria value 

(http://water.epa.gov/scitech/swguidance/standards/handbook/index.cfm ) 

4.3 Exposure Analysis Plan 

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates 

In order to address the risk hypothesis, the potential for adverse effects on the environment will 

be estimated. For down-the-drain (DtD) risk estimates, an approach that estimates the number of 

days a concentration-of-concern (COC) is exceeded, also referred to as a probabilistic dilution 

model (PDM) approach, is used to assess risk to aquatic organisms. The environmental fate and 

effects data anticipated to be needed to conduct a more refined DtD assessment are provided as 

part of the work plan. 

This analysis plan will be revisited and may be revised depending upon a full review of the data 

available in the open literature and the information submitted by the public in response to the 

opening of the Registration Review docket. 

4.3.2 Down-the-Drain Analysis 

Data received in response to the data call-in expected to be issued as part of this registration 

review will allow the Agency to estimate potential down-the-drain exposure. 
Page 31 of 80

4.4 Effects Analysis Plan 

Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) 

database5, which employs a literature search engine for locating chemical toxicity data for 

aquatic life, terrestrial plants, and wildlife. The ECOTOX database will be searched when the 

risk assessment for chlorinated isocyanurates is prepared. At that time, open literature studies 

will be reviewed that potentially provide data for missing or modeled endpoint values or provide 

a value more sensitive than what is available in-house. 

Data from an ECOTOX run for chlorinated isocyanurates and their degradates will be evaluated 

for possible quantitative and/or qualitative inclusion in the risk assessment in support of 

Registration Review. Data are obtained from registrant-submitted studies or from literature 

studies identified by ECOTOX. The ECOTOX database provides more ecological effects data in 

an attempt to bridge existing data gaps and uncertainties. ECOTOX is a source for locating 

single chemical toxicity data and potential chemical mixture toxicity data for aquatic life, 

terrestrial plants, and wildlife. ECOTOX was created and is maintained by the USEPA, Office of 

Research and Development, and the National Health and Environmental Effects Research 

Laboratory's Mid-Continent Ecology Division. 

5 Endocrine Disruptor Screening Program (EDSP) 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of a 2001, registration action for chlorinated isocyanurates, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

chlorinated isocyanurates are subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

 

5

 http://cfpub.epa.gov/ecotox/ 
Page 32 of 80

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. The chlorinated 

isocyanurates are not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue future 

EDSP orders/data call-ins, requiring the submission of EDSP screening assays for the 

chlorinated isocyanurates. For further information on the status of the EDSP, the policies and 

procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening 

battery, please visit our website: http://www.epa.gov/endo/. 

6 Next Steps 

EPA will issue a DCI for the Chlorinated Isocyanurates Case. 

7 References 

Anderson, K.L., K.A. Wheeler, J.B. Robinson, and O.H. Tuovinen. 2002. Atrazine 

Mineralization Potential in Two Wetlands. Water Research 36: 4785-4794. 

Cook, A., P. Beilstein, J. Grossenbacher, and R. Hütter. 1985. Ring cleavage and degradative 

pathway of cyanuric acid in bacteria, Biochem. J., 1985, 231, 25-30. 

Dufour, A, O. Evans, T. Behymer, and R. Cantú. 2006. Water ingestion during swimming 

activities in a pool: a pilot study. Journal of Water & Health, 4, 425-430. 

Ellis DD et al. 1982. Arch Environ Contam Toxicol 11: 373 - 82. 

Ernst, C., and H. Rehm. 1990. Degradation of Cyanuric Acid by Immobilized Bacteria, , 

DECHEMA Biotechnol. Conf., 4(Pt. A), 577-580. 

Helfgott, T., F. Hart and R. Bedard. 1977. An Index of Refractory Organics, EPA 600/2-77-

174,, pp. 1-7, 24-25. 

Hu, H.C. 1981a. Hydrolysis Study of Aqueous Sodium Salt Solutions of 2,4,6-Trihydroxy-1,3,5-

triazine. (Unpublished study received Jan 26, 1981 under unknown admin. no.; prepared 

by FMC Corp., submitted by Monsanto Co., Washington, D.C.; CDL:244259-A). MRID 

00056478 
Page 33 of 80

Hu, H.C.; 1981b. Photodegradation Study of Aqueous Sodium Salt Solutions of 2,4,6-

Trihydroxy -1,3,5-Triazine; Unpublished Study Conducted by Center Analytical 

Services, Princeton Chemical Research & Development Center, Princeton, NJ 08540 for 

the Isocyanurate Industry Ad Hoc Committee (EPA Consortium 55643); Study No. 

(none), January 21, 1981. MRID 00056479. 

IHS Chemical Economics Handbook. 2012. Chlorinated Isocyanurates. IHS Chemical 

Jessee, J., R. Benoit, A., Hendricks, G. Allen, and J. Neal. 1983. Anaerobic Degradation of 

Cyanuric Acid, Cysteine, and Atrazine by a Facultative Anaerobic Bacterium, Appl. and 

Environ. Microbiol. 45(1) 97-102. 

Kontchou, C.Y and N. Gschwind. 1999. Biodegradation of S-Triazine Compounds by a Stable 

Mixed Bacterial Community. Ecotoxicology and Environmental Safety 43: 47-56. 

Michael, P., and Cummings, I. 1982. Cyanuric Acid Absorption On Soils, Monsanto Report ES82-SS-94. Method: OECD 106. 

Saldick, J. 1974. Biodegradation of Cyanuric Acid, Applied Microbiology 28(6) 1004-1008. 

Sisodia,, S., A. Weber, and J. Jensen, 1996. Continuous Culture Biodegradation of Simazine’s 

Chemical Oxidation Products, Water Research 30(9) 2055-2064. 

Soto, AM et al. 1995. The E-Screen Assay as a Tool to Identify Estrogen - An Update on 

Estrogenic Environmental Pollutants, Environmental Health Perspectives, Vol. 103, 

Supplement 7, pp 113-122. 

United States Environmental Protection Agency (USEPA). High Production Volume 

Information System (HPVIS). http://www.epa.gov/hpvis/ 

USEPA. 1988. Guidance for the Reregistration of Pesticide Products Containing Chlorinated 

Isocyanurates as the Active Ingredient, 540/RS-88-077, PB88-220660. 83 pp. 

http://nepis.epa.gov/Exe/ZyNET.EXE?ZyActionL=Register&User=anonymous&Passwor

d=anonymous&Client=EPA&Init=1

USEPA. 1985. Ambient Water Quality Criteria for Chlorine - 1984. Office of Water 

Regulations and Standards Criteria and Standards Division, EPA 440/5-84-030. 

http://water.epa.gov/scitech/swguidance/standards/upload/2001_10_12_criteria_ambient

wqc_chlorine1984.pdf

USEPA. 1992. Registration Eligibility Document (RED): Chlorinated Isocyanurates. 

USEPA/Pesticides and Toxic Substances (H-7508W), September, 1992. 

http://www.epa.gov/oppsrrd1/REDs/old_reds/chlorinated_isocyanurates.pdf
Page 34 of 80

Yamasaki et al. 2003. Immature Rat Uterotrophic Assay of 18 Chemicals and Hershberger 

Assay of 30 Chemicals. Toxicology 183, pp 93-115, 2003. 

Zeyer, J., R. Hütter, and P. Mayer. 1980. Process for the biological degradation of cyanuric 

acid, UK Patent App. 2,025,919 (Jan. 30, 1980). 
Page 35 of 80

Appendix A: Environmental Fate 

The Agency has reviewed environmental fate data submitted in support of registration review 

from submitted OCSPP 835 laboratory studies, the EPI-WEB 4.0 program, and the open 

literature. Many of these literature sources were included in the High Production Volume (HPV) 

submissions (http://www.epa.gov/hpv/pubs/summaries/tricltrz/c14659rs.pdf ). These data 

sources indicate that the parent compounds trichloro- and dichloro isocyanurates readily 

dechlorinate in water to form the active ingredient hypochlorous acid and the degradates 

cyanuric/isocyanuric acid (symmetrical triazine ring tautomers with readily-interchangeable keto 

or enol groups depending on pH). Cyanuric and isocyanuric acids are highly water soluble, 

weakly sorbed, and will be in the water phase in both soil and waste water treatment plants 

(WWTPs). Cyanuric/isocyanuric acids degradates do not degrade under abiotic conditions 

(presence of water and/or light without microorganisms). However, cyanuric/isocyanuric acid is 

generally more degradable under anaerobic conditions in the presence of microorganisms 

(acclimated or unacclimated) or when acclimated microorganisms are present under aerobic 

conditions. The ultimate breakdown products of cyanuric acid are CO2 and NH3, both of which 

can be released into air or incorporated into microbial biomass. The environmental fate 

properties of trichloro isocyanuric acid and its metabolites are summarized in Table 12. 

Cyanuric/Isocyanuric Acids

Trichloro isocyanuric acid and triazine herbicides share a symmetric triazine ring. However, the 

agronomic herbicides that are classified as s-triazine compounds have alkyl side chains. 

Trichloro isocyanuric acid is not considered as part of the triazine cumulative assessment (See 

Section 4.2). Therefore, a total toxic residue approach, as would be used for s-triazine 

compounds, will not be applied to assess environmental exposure. Trichloro isocyanuric acid 

dechlorinates to form the cyanuric acid and isocyanuric acid metabolites. These metabolites, 

which are tautomers, are the compounds of potential concern based on the environmental fate 

data based on their environmental persistence. Under anaerobic conditions (acclimated or 

unacclimated microorganisms) and also aerobic conditions with acclimated microorganisms, 

these metabolites can be further degraded into CO2 and NH3, both of which can be released into 

air or incorporated into microbial biomass. 

Chlorinated isocyanurates (parent compounds) are used in water treatment to form hypochlorous 

acid (an oxidizing agent) when dissolved in water. Hypochlorous acid is a weak acid because it 

has a pKa (dissociation constant) of 3.7 x 10-8) at 25 o

C. Based on this pKa, 50% will be in 

hypochlorous acid form (HOCl) and 50% will be in hypochlorite ion (-OCl) form at pH 7.4 (pH 

= -log10 (3.7 x 10-8). As the pH increases above 7.4, the amount of hypochlorite ion present will 

increase. Conversely, as the pH decreases below pH 7.4, the amount of hypochlorous acid 

present will increase. Hypochlorous acid reacts readily with ammonia, amines, sulfides, sulfites, 

and nitrites present in the water. Antimicrobial activity results from the oxidation reactions 

with microbial enzyme systems. All these oxidation reactions consume residual free 
Page 36 of 80

chlorine, with the concurrent reduction of hypochlorous acid/hypochlorite to chloride anions. 

However, the release of hypochlorous acid is reversible and it can reattach to the 

cyanuric/isocyanuric acid if additional free hypochlorous acid is added. 

The chlorinated isocyanurate degradates, cyanuric acid and isocyanuric acid (dechlorinated 

parent compound) exist in a pH-dependent equilibrium. These two acids are keto/enol tautomers 

which interconvert readily depending on the pH of the environment. The cyanuric acid (enol 

form with three hydroxyl groups (-OH) attached to triazine ring) is the primary form found at 

lower pH values, while the isocyanuric acid (keto form, with three oxygens double-bonded with 

triazine ring) would be found at higher pH values. The pKa values for cyanuric acid are 6.88, 

11.4, and 13.5 (http://www.drugfuture.com/chemdata/cyanuric-acid.html ). 

Hu (1981a.b) found that cyanuric/isocyanuric acid is not prone to abiotic degradation (hydrolysis 

or direct photolysis in water). Microbial degradation of cyanuric/isocyanuric acid was variable 

and depended on the level of oxygenation and the presence of acclimated microorganisms. 

Cyanuric/isocyanuric acid degrades more quickly under anaerobic conditions than under aerobic 

conditions. Degradation under aerobic conditions, however, is accelerated in the presence of 

acclimated microorganisms. 

There are data available on the metabolism of the triazine ring from studies conducted with 

trichloro isocyanuric acid and from studies with the s-triazine herbicide atrazine, which like 

cyanuric/isocyanuric acid, contains a symmetric triazine ring. Mineralized cyanuric/isocyanuric 

acid forms CO2 and NH3 which can enter the air or microbial biomass (Saldick, 1974; Ernst and 

Rehm, 1990; Jessee et al., 1983; Cook et al., 1985; Zeyer et al., 1980). In artificial and natural 

wetlands and in river water draining atrazine-treated corn fields, degradation of atrazine occurred 

by acclimated microorganisms (Anderson et al., 2002). Most atrazine (60-81 %) was ultimately 

degraded (mineralized) to CO2 and NH3. The remaining applied atrazine was present in the form 

of cyanuric acid. However, in a Cedar Bog wetland with no previous exposure of 

microorganisms to atrazine, very limited atrazine mineralization was observed. In a laboratory 

biodegradation study (Kontchou and Gschwind, 1999), most s-triazine herbicides were readily 

metabolized to cyanuric acid, which did not readily degrade. These results indicate that the 

microorganisms in this study were not acclimated to cyanuric acid. Therefore, if atrazine 

mineralizes in a stream with acclimated microorganisms, then cyanuric acid would also be 

expected to mineralize because they both share a symmetric triazine ring.

Bioconcentration of the cyanuric/isocyanic acid metabolites in mammals, fish, or non-target 

aquatic organisms is not expected to be significant. This conclusion is based on the relatively 

low Log Kow (1.95), which is less than the level of concern (3.0). Also, these metabolites have 

a water solubility of approximately 2,000 mg/l (ppm) [EPI-WEB 4.0]. 

There are some outstanding environmental fate data requirements for the degradate 

cyanuric/isocyanuric acid to support Registration Review, and the anticipated need for these data 
Page 37 of 80

is based on the unknown relevance of the WWTP degradation results in the HPV document. The 

Agency expects to require the registrant to submit these studies on the fate of trichloro- and 

dichloro- cyanuric acid degradates on sewage treatment to satisfy the relevant data requirements 

listed below. They can be submitted to OPP for review to meet the data requirements. 

Trichloro- and di-chloro- isocyanuric acids (parent compounds) degrade rapidly by hydrolysis to 

form cyanuric and isocyanuric acids (CAS 108-80-5), which are stable in the absence of 

microorganisms and under most aerobic conditions in the presence of microorganisms. Because 

of this rapid hydrolysis to cyanuric acid, photodegradation of parent compounds in water (a 

competing environmental dissipation route) is not a significant route of degradation. The 

Agency's in-house database does not have any acceptable environmental fate and transport data 

on cyanuric acid. These data are anticipated to be required to assess environmental fate for the 

registered use patterns that may potentially enter waste water treatment plants (WWTPs) and 

subsequently be discharged to aquatic environments. An examination of the chemical structure, 

open literature from Science Direct (Anderson, 2002; Kontchou and Gschwind, 1999, Table 12), 

and a review of information in a Robust Summary in the HPV documentation 

(http://www.epa.gov/hpv/pubs/summaries/tricltrz/c14659rs.pdf, Table 12) indicates that a high 

percentage (up to 100 %) of cyanuric acid may be removed either by aerobic WWTPs using 

acclimated microorganisms or WWTPs using anaerobic conditions (acclimated or unacclimated 

microorganisms). The primary removal mechanism was attributed to mineralization because (1) 

there was no evidence of sorption to sludge based on the low log Kow (1.95) and water solubility 

(2,000 mg/l) and (2) the study authors reported the release of CO2 and ammonia (NH3) or the 

incorporation of these substances into microbial biomass. 

To be able to give merit to this claim of mineralization, the Agency would need to review and 

evaluate the primary references cited in the HPV documentation. Without reviewing and 

evaluating these primary references and reaching the same conclusions as those presented, the 

Agency anticipates needing environmental fate data from tests including the studies listed below. 

o Anaerobic aquatic metabolism for the degradate cyanuric acid (GLN 835.4400); 

o Aerobic aquatic metabolism for the degradate cyanuric acid (GLN 835.4300); 

o Activated Sludge Respiration Inhibition (ASRI, OECD 209) or Modified ASRI 

test (850.3300) 

o Ready biodegradability (GLN 835.3110), or Porous Pot Test (GLN 835.3220), or 
Page 38 of 80

Simulation Tests to Assess the Biodegradability of Chemicals Discharged to 

Wastewater (GLN 835.3280), or Simulation Test – Aerobic Sewage Treatment: 

A. Activated Sludge Units (GLN 835.3240) for cyanuric acid6

. 

Table 12 Environmental Fate Data for Chlorinated Isocyanurates (di- and tri-chloro) 

Test Guideline 

(Number) 

Test Substance Result Reference Comment 

Hydrolysis 

(835.2120) 

Isocyanuric acid 

and sodium 

isocyanurate 

Rapid degradation to cyanuric 

acid 

Hu, 1981a 

MRID 00056478 

Cyanuric acid was stable

Not mentioned in HPV 

document1

Photodegradation 

in Water 

(835.2240) 

Monosodium 

cyanurate 

Rapid degradation to cyanuric 

acid from hydrolysis (no 

photodegradation)_ 

Hu, 1981b 

MRID 00056479 

Cyanuric acid was stable

pp. 10-12 of HPV 

document1

Batch Equilibrium 

(835.1230, OECD 

106) 

Cyanuric acid Average Koc of 51 ml/g Michael and 

Cummings, 1982 

Similar to OECD 106 

Unknown Cyanuric acid Aerobic Conditions 

Degrades slowly under aerobic 

conditions. 

Some microorganisms can 

degrade cyanuric acid if 

acclimated and organic 

nutrients are present 

Anaerobic conditions 

Readily biodegradable 

Zeyer et al., 1980 Cyanuric acid formed 

CO2 and NH3 

p. 15 of HPV document 

Unknown Cyanuric acid Aerobic conditions 

30 and 15 % degradation of 

cyanuric acid in 48 h for 

Pseudomonas sp. And 

Achromobacter sp. 

Ernst and Rehm. 

1990 

Cyanuric acid formed 

CO2 and NH3 

pp. 17-18 of HPV 

document 

Bacteria isolated from 

corn field 

 

6

 The results of the Activated Sludge Respiration Inhibition Test (ASRI) determine which of these biodegradation 

tests are required. If the ASRI test EC50 is less than or equal to 20 mg/L, then either the Biodegradation in Activated 

Sludge Study or the Porous Pot Test is required. If the ASRI test EC50 is greater than 20 mg/L, then the applicant 

must choose either: (i) Ready Biodegradability or (ii) Biodegradation in Activated Sludge or the Porous Pot Test. If 

the antimicrobial passes the ready biodegradability study, then no further testing is required. If, however, the 

antimicrobial fails the ready biodegradability study, then the Biodegradation in Activated Sludge or the Porous Pot 

study is required. 
Page 39 of 80

Test Guideline 

(Number) 

Test Substance Result Reference Comment 

Unknown Cyanuric acid 

Aerobic conditions 

58 % degradation of cyanuric 

acid in 8 days in FeS medium 

under aerobic conditions 

Anaerobic conditions 

100 % degradation of cyanuric 

acid in 4 days under anaerobic 

conditions in cysteine medium

Jessee et al., 1983 Unknown bacterium 

from acclimated bottom 

sediment downstream of 

WWTP in Illinois that 

treats wastewater from 

trichloro isocyanuric 

acid manufacturing 

facility 

Cyanuric acid formed 

CO2 and NH3 

pp. 19-20 of HPV 

document 

Unknown Cyanuric acid Anaerobic conditions 

100 % degradation of triazine 

ring when additional source of 

nitrogen was present 

No cell growth in absence of 

additional nitrogen source 

Cook et al., 1985 Pseudomonas NRRL B12227 and B-12228 and 

Klebsiella pneumoniae 

Cyanuric acid formed 

CO2 and NH3 

pp. 21-22 

Unknown Cyanuric acid Aerobic conditions 

100% degradation after 8 h 

(aerated activated sludge, 2.5 

mg/l O2) 

42% degradation after 9 h 

(aerated activated sludge, 8.7 

mg/l O2) 

0 % degradation (highly 

aerobic system, O2

concentration not specified) 

Anaerobic conditions 

25-50% degradation in 48 h 

and 100 % in 72 h (sewage) 

95-98 % degradation in 72 h 

(nutrient broth) 

52-100 % degradation in 9-23 

days (6 soils and muds) 

Saldick, 1974 Cyanuric acid formed 

CO2 and NH3 

pp. 22-23 of HPV 

document 
Page 40 of 80

Test Guideline 

(Number) 

Test Substance Result Reference Comment 

Unknown Cyanuric acid 100 % degradation in unknown 

time 

Sisodia et al., 

1996 

Degradation of cyanuric 

acid occurs in absence of 

nitrogen when triazineacclimated bacteria are 

present 

Cyanuric acid formed 

CO2 and NH3 

pp. 24-25 of HPV 

document 

Unknown Cyanuric acid BOD5 and COD of 6.5 and 11 

mg/l 

Unknown 

reference, possibly 

Zeyer et al., 1980 

p. 15 of HPV document 

Aerobic Aquatic 

Metabolism 

(835.4300) 

Atrazine 70-80 % of atrazine 

mineralization in constructed 

wetland fed by river draining 

treated corn fields 

Wetland water demonstrated 

60-80 % of atrazine 

mineralization in one month 

75-81 % mineralization in river 

water samples containing 

acclimated microorganisms 

Cedar bog did not demonstrate 

mineralization of atrazine 

because microorganisms were 

not adapted 

Anderson et al., 

2002 

Atrazine acid totally 

mineralized in the river 

and constructed wetland 

that contained 

microorganisms that are 

acclimated to 

degradation of triazine 

rings from herbicides. 

Atrazine did not 

mineralize in wetland 

without acclimated 

microorganisms. 

Atrazine formed CO2

and NH3

None Numerous 

triazine 

herbicides 

Cyanuric acid was end product 

(degradate) of S-triazines that 

reached WWTPs and was not 

degraded significantly 

Kontchou and 

Gschwind, 1998 

Mixed culture of 

microorganisms in 

laboratory test. 

1. HPV, http://www.epa.gov/hpv/pubs/summaries/tricltrz/c14659rs.pdf 

Hypochlorous Acid

Chlorinated isocyanurates (parent compounds) are used in water treatment to form 

hypochlorous acid (HClO), an oxidizing agent. When dissolved in water the chlorinated 

isocyanurates rapidly hydrolyze to release free chlorine and a complex series of equilibria of 

chlorinated and non-chlorinated isocyanurates. The concentration of each entity depends on the 

concentration of total available chlorine (free available chlorine plus “reservoir” or bound 

chlorine), total isocyanurate concentration, and pH. It is HClO which is the active disinfection 

moiety for all hypochlorites in aqueous medium and is the most effective form of what is called 

free chlorine residual, which is chlorine available to kill microorganisms. The trichloro form has 

three chlorine molecules which can be released, and the dichloro has two. 

HClO is a weak acid and depending upon pH can further breakdown or disassociate into a proton 

or hydrogen ion and a hypochlorite ion (ClO-

), the reaction is reversible. The antimicrobial 
Page 41 of 80

activity of chlorine compounds depends primarily on HClO which can rapidly cross cell 

membranes. While ClO-

 has some disinfection potential it requires longer contact time. 

HClO

ு௬௣௢௖௛௟௢௥௢௨௦ ௔௖௜ௗ

 

ርۛۛሮ H൅

ு௬ௗ௥௢௚௘௡ ௜௢௡

൅ ClO‐

ு௬௣௢௖௛௟௢௥௜௧௘ ௜௢௡

o The acid dissociation constant (Kdiss or Ka) of HClO is 3.4 x 10-8 (or pKa

7

 = 7.7). 

Hence at any given time, the concentration of HClO is not very high; however, as 

it gets used up—more HClO is formed and so on. It also means that at pH 7.7, the 

ratio of HClO to ClO-

 is 50:50, while at pH 7.2, 70% is HClO and 30% is ClO-. 

o A literature report (Connell, 1996) estimated the changes due to protolysis 

(hydrolysis) of a solution containing ClO-

. The graphical data is converted into 

the numerical data on the percent of HClO and ClO- from pH 4 to 11 as shown in 

the table below. In dilute aqueous solutions these reactions occurs in seconds or 

even in less time. This is typical of inorganic reactions. 

pH Percent HClO Percent ClO4.0 100

6.3 95 5

7.2 70 30

7.7 50 50

8.0 21 79

11 100

o Disinfection is more efficient at lower pH than at higher pH because HClO is a 

more efficient disinfectant than ClO-, and as indicated above there is a higher 

proportion of HClO at lower pH than at higher pH values. 

 It is ClO- and/or HClO moieties that are the active antimicrobial portion of the 

chlorinated isocyanurates. 

 Available chlorine (AC) is a measure of the equivalent weights of oxidizing agents, with 

chlorine gas as a basis—i.e., normalizes chlorine-containing compounds to allow 

comparison of oxidizing potential. The concentration of hypochlorite (or any other 

oxidizing disinfectant) may be expressed as available chlorine by determining the 

electrochemical equivalent amount of elemental chlorine (Cl2) to that compound (USEPA 

1986). 

o A mole of chlorine gas reacts with water to form a mole of HClO and a mole of 

protons (or hydrogen ions) and a mole of chloride ions. The oxidation state of 

chlorine is 0 in chlorine gas, +1 in HClO and -1 in Cl-

; therefore chlorine is both 

oxidized and reduced in this reaction. 

Cl2

஼௛௟௢௥௜௡௘, ௚௔௦

൅ H2O

ௐ௔௧௘௥

 

ሱۛሮ HClO

ு௬௣௢௖௛௟௢௥௢௨௦ ௔௖௜ௗ

൅ H൅

ு௬ௗ௥௢௚௘௡ ௜௢௡

൅ Cl‐

஼௛௟௢௥௜ௗ௘ ௜௢௡

o Elemental Cl2 oxidizing potential: one mole of elemental chlorine is capable of 

reacting with two electrons to from inert chloride, as shown in the reaction 

 

7

 pKa = -log10Ka
Page 42 of 80

equation below (USEPA, 1986). The AC is 70.91 grams per mole (identical to 

the molecular weight of Cl2). 

Cl2

஼௛௟௢௥௜௡௘

൅ 2݁ି

ா௟௘௖௧௥௢௡௦

ൌ 2Cl‐

஼௛௟௢௥௜ௗ௘ ௜௢௡

o ClO-

 oxidizing potential: one mole of ClO- may react with two electrons to form 

chloride, as shown in the reaction equation below. Hence, one mole of 

hypochlorite is equivalent (electrochemically) to one mole of elemental chlorine, 

and may be said to contain 70.91 grams of AC (identical to the molecular weight 

of Cl2) (USEPA, 1986). 

ClOି

ு௬௣௢௖௛௟௢௥௜ௗ௘

൅ 2݁ି

ா௟௘௖௧௥௢௡௦

൅ 2H൅

ு௬ௗ௥௢௚௘௡ ௜௢௡

ൌ Cl‐

஼௛௟௢௥௜ௗ௘ ௜௢௡

൅2H2O

ௐ௔௧௘௥

o The free available chlorine as a percent by weight for each of the chlorinated 

isocyanurates in this registration review is theoretically: 

Chemical 

Name Sodium dichloro-s-triazinetrione Trichloro-s-triazinetrione Sodium dichloro-s-triazinetrione dihydrate 

Available 

Chlorine (%) 63 90 56 

 Chlorine in addition to providing disinfection or oxidation of microorganisms can be 

consumed by oxidation or substitution reactions with inorganic substances such as 

ammonia, iron, manganese, sulfides and some other organic substances (e.g., phenols). 

 In the surface water and wastewater streams possible transformation products like 

chlorine, HOCl, ClO3

-

 may be present, but the determination of exact amounts of these 

moieties cannot be calculated as these will depend on the environmental conditions like 

pH of the medium, temperature, ionic strength, etc. 

Appendix A References 

Anderson, K.L., K.A. Wheeler, J.B. Robinson, and O.H. Tuovinen. 2002. Atrazine 

Mineralization Potential in Two Wetlands. Water Research 36: 4785-4794. 

Cook, A., P. Beilstein, J. Grossenbacher, and R. Hütter. 1985. Ring cleavage and degradative 

pathway of cyanuric acid in bacteria, Biochem. J., 1985, 231, 25-30. 

Ernst, C., and H. Rehm. 1990. Degradation of Cyanuric Acid by Immobilized Bacteria, , 

DECHEMA Biotechnol. Conf., 4(Pt. A), 577-580. 

Hu, H.C. (1981a) Hydrolysis Study of Aqueous Sodium Salt Solutions of 2,4,6-Trihydroxy1,3,5-triazine. (Unpublished study received Jan 26, 1981 under unknown admin. no.; 

prepared by FMC Corp., submitted by Monsanto Co., Washington, D.C.; CDL:244259-

A). MRID 00056478 
Page 43 of 80

Hu, H.C. (1981b) Photodegradation Study of Aqueous Sodium salt Solutions of 2,4,6-

Trihydroxy-1,3,5-triazine. (Unpublished study received Jan 26, 1981 under unknown 

admin. no.; prepared by FMC Corp., submitted by Monsanto Co., Washington, D.C.; 

CDL: 244259-B). MRID 00056479 

Jessee, J., R. Benoit, A., Hendricks, G. Allen, and J. Neal. 1983. Anaerobic Degradation of 

Cyanuric Acid, Cysteine, and Atrazine by a Facultative Anaerobic Bacterium, Appl. and 

Environ. Microbiol. 45(1) 97-102. 

Kontchou, C.Y and N. Gschwind. 1999. Biodegradation of S-Triazine Compounds by a Stable 

Mixed Bacterial Community. Ecotoxicology and Environmental Safety 43: 47-56. 

Michael, P., and Cummings, I. 1982. Cyanuric Acid Absorption On Soils, Monsanto Report ES82-SS-94. Method: OECD 106. 

Saldick, J. 1974. Biodegradation of Cyanuric Acid, Applied Microbiology 28(6) 1004-1008. 

Sisodia,, S., A. Weber, and J. Jensen, 1996. Continuous Culture Biodegradation of Simazine’s 

Chemical Oxidation Products, Water Research 30(9) 2055-2064. 

Zeyer, J., R. Hütter, and P. Mayer. 1980. Process for the biological degradation of cyanuric 

acid, , UK Patent App. 2,025,919 (Jan. 30, 1980). 
Page 44 of 80

Appendix B: Toxicology Profile 

Hazard/Toxicity 

The most recent review of the toxicity data for the chlorinated isocyanurates was included in the 

HIARC report of January 25, 2001. This report also re-affirmed the conclusion from the RED 

that toxicology data on isocyanuric acid would support assessment of hazard from exposure to 

the chlorinated derivatives. In RED, which was written in 1992, the Agency stated that for 

purposes of hazard assessment, the isocyanurates could be divided into three groups for acute 

toxicity testing (isocyanuric acid, dichloroisocyanurates, and trichloroisocyanurates), while for 

subchronic, chronic, developmental, mutagenicity, and metabolism testing, the Agency 

determined that isocyanuric acid could represent all of the chlorinated isocyanurates. The 

Agency justified this approach at that time, stating that “since the chronic effects of chlorine for 

humans are well known, EPA determined that isocyanuric acid can represent all the chlorinated 

isocyanurates for the purpose of conducting metabolism, subchronic, chronic, developmental, 

and mutagenicity studies.” 

No additional studies have been submitted to the Agency and no public literature was found that 

was dated after the HIARC report was written.

Acute Toxicity for Product Labeling 

The acute toxicity profile for isocyanuric acid, as represented by data on the chlorinated 

isocyanurate compound trichloro-s-triazinetrione, is listed in Table 13. The acute toxicity is 

minimal by the oral, dermal, and inhalation routes of exposures, (Toxicity Category III for oral 

and dermal, Toxicity Category IV for inhalation). However, the isocyanurates demonstrate 

significant irritation to the skin and eyes (Toxicity Category I) and are also dermal sensitizers. 

Table 13 - Acute Toxicity of the Chlorinated Isocyanurates 

Guideline 

No. Study Type MRIDs # Results Toxicity Category

81-1 Acute Oral 00150959 LD50 = 787 mg/kg (M) and 868 mg/kg (F) III 

81-2 Acute Dermal 42180403 LD50 > 2000 mg/kg III 

81-3 Acute Inhalation LC50 > 200 mg/L IV 

81-4 Primary Eye Irritation 00019754 severe eye irritant I 

81-5 Primary Skin Irritation 00019754 severe dermal irritant I 

81-6 Dermal Sensitization 00144720 dermal sensitizer 

81-8 Acute Neurotoxicity N/A N/A 

Subchronic Toxicity 

In subchronic toxicity tests (MRIDs #0063477 and MRID #00124782), the dose levels in rats 

and mice at which toxicity is manifested are considered high (LOAELs of 672 mg/kg/day in rats, 
Page 45 of 80

LOAEL > 1994 mg/kg/day in mice). There were no reported signs of toxicity after 13-week 

administration of the test chemical to mice, and in rats, toxicity was manifested in the urinary 

bladder as hyperplasia of the urinary bladder epithelium, a known toxic response to 

isocyanurates at high dose levels as a result of precipitation of the chemical in the bladder. 

Developmental and Reproductive Toxicity 

In developmental toxicity tests, isocyanuric acid at doses up to 500 mg/kg/day in rabbits (MRID 

#42054101) and 5000 mg/kg/day in rats (MRID #00105168) caused no significant maternal or 

developmental toxicity. 

In reproductive toxicity testing, isocyanuric acid produced calculi in the urinary bladder in 

parental rats of the F2 generation at doses approximating a limit dose of 1000 mg/kg/day, while 

there were no reported reproductive or fertility effects in offspring of any generation at doses up 

to and including a limit dose of 1000 mg/kg/day (MRID #00150286). In one study with 

monosodium isocyanurate in rabbits (MRID #42054101), increased fetal and litter incidence of 

hydrocephaly was observed in offspring at a dose of 500 mg/kg/day, a dose which was not 

maternally toxic. The weight of the evidence suggests no developmental or reproductive toxicity 

from exposure to isocyanuric acid, but the results of the single rabbit study must also be 

considered. 

Chronic Toxicity and Carcinogenicity 

Isocyanuric acid has been adequately tested for chronic toxicity and carcinogenicity in studies 

with rats (MRID #00126362) and mice (MRID #00126361). In both of these studies, 

isocyanuric acid was found to be devoid of carcinogenic effects. Although epithelial hyperplasia 

was observed in the rat study, this is known to be a result of calculi formation in male rat bladder 

as a result of precipitation of the test chemical in urine at high doses and as a result of the pH of 

rodent urine. 

Mutagenicity 

The negative results of carcinogenicity testing are supported by the results of mutagenicity 

testing (MRIDs #0094883, #0091031 and #0094882) of isocyanuric acid that shows the chemical 

to be negative in all mutagenicity assays submitted to the Agency. 
Page 46 of 80

Appendix C: Ecotoxicology Profile 

 A review of toxicity effects data for the chlorinated isocyanurates is summarized 

in the following sections, with selected ecotoxicological endpoints for risk 

assessment provided in Table #11. As discussed in the fate section, the 

chlorinated isocyanurates in aqueous solution will release chlorine forming 

hypochlorous acid and the isocyanuric acid/cyanuric acid degradate. Therefore 

for aquatic organisms, toxicity information on both the chlorinated isocyanurates 

or chlorine as surrogate and the isocyanuric acid degradate is used to assess risks. 

Terrestrial - Avian acute-oral and dietary toxicity-Chlorinated Isocyanurates

An acute oral toxicity study using the technical grade of the active ingredient (parent 

compounds, i.e. TGAI) is anticipated to be required to establish the toxicity of the chlorinated 

isocyanurates to birds. The preferred test species is either the mallard (Anas platyrhynchos) or 

the northern bobwhite (Colinus virginianus). Data for both mallard and northern bobwhite have 

been submitted for trichloro-s-triazinetrione (Table 14), sodium dichloroisocyanurate dihydrate 

(Table 15), and sodium dichloro-s-triazinetrione (Table 16). Those 7 studies categorize the 

chlorinated isocyanurates as being slightly to practically nontoxic to birds on an acute-oral basis 

(LD50’s = 1021 to >2250 mg ai/kg-bw). The data requirement (850.2100) is satisfied. Chronic 

data (850.2300) are not expected to be required. 

Avian dietary toxicity studies (850.2200) are not expected to be required for the current uses. 

However, a total of 12 studies were submitted for trichloro-s-triazinetrione, sodium dichloro-striazinetrione, and sodium dichloroisocyanurate dihydrate for both mallard and northern 

bobwhite. Those data categorize the chlorinated isocyanurates as being practically non-toxic to 

birds on a dietary basis (LC50’s >5000 ppm). 

Table 14 Available Endpoints from Avian Ecotoxicity Studies for Trichloro-striazinetrione 

Study Type Species 

Test 

material 

(% ai) 

Toxicity1 Toxicity 

Classification 

MRID & 

Status 

Acute – Avian 

Oral 

850.2100 

Northern 

bobwhite 

92 LD50: 1674 mg/kg-bw/day Slightly toxic 00150962 

Acceptable 

99 LD50: >2250 mg/kg-bw/day Practically 

nontoxic 

00144303 

Supplemental 

Mallard 

100 LD50: 1890 mg/kg-bw/day Slightly toxic 00132603 

Supplemental 

100 LD50: 1021 mg/kg-bw/day Slightly toxic 00126521 

Acceptable 

Acute – Avian 

Dietary 

850.2200 

Northern 

bobwhite 100 LC50: 7235 ppm Practically 

nontoxic 

0019380 & 

00132427 

Acceptable 
Page 47 of 80

Study Type Species 

Test 

material 

(% ai) 

Toxicity1 Toxicity 

Classification 

MRID & 

Status 

92 LC50: >5000 ppm Practically 

nontoxic 

00150964 

Acceptable 

99 LC50: >5000 ppm Practically 

nontoxic 

00144302 

Supplemental 

Mallard 

100 LC50: >10,000 ppm Practically 

nontoxic 

00132426 

Acceptable 

92 LC50: >5000 ppm Practically 

nontoxic 

00150963 

Supplemental 

99 LC50: >5620 ppm Practically 

nontoxic 

00144301 

Supplemental 1

 Toxicity values based on parent compound (TGAI). 

Table 15 Available Endpoints from Avian Ecotoxicity Studies for Sodium 

Dichloroisocyanurate Dihydrate 

Study Type Species 

Test 

material 

(% ai) 

Toxicity Toxicity 

Classification 

MRID & 

Status 

Acute – Avian 

Oral 

850.2100 

Northern 

bobwhite 98.3 LD50: 1766 mg/kg-bw/day Slightly toxic 00150947 

Acceptable 

Acute – Avian 

Dietary 

850.2200 

Northern 

bobwhite 98 LC50: >5000 ppm Practically 

nontoxic 

00150949 

Acceptable 

Mallard 98 LC50: >5,000 ppm Practically 

nontoxic 

00150948 

Acceptable 1

 Toxicity values based on parent compound (TGAI). 

Table 16 Available Endpoints from Avian Ecotoxicity Studies for Sodium Dichloro-sTriazinetrione 

Study Type Species 

Test 

material 

(% ai) 

Toxicity Toxicity 

Classification MRID & Status 

Acute – Avian 

Oral 

850.2100 

Northern 

bobwhite 98 LD50: >2250 mg/kg-bw/day Practically 

nontoxic 

00144306 

Acceptable 

Mallard 100 LD50: 1915 mg/kg-bw/day Slightly toxic 00125993 

Supplemental2

Acute – Avian 

Dietary 

850.2200 

Northern 

bobwhite 

98 LC50: >5600 ppm Practically 

nontoxic 

001444305 

Acceptable 

100 LC50: >10,000 ppm Practically 

nontoxic 

0019608 

Acceptable 

Mallard 100 LC50: >10,000 ppm Practically 

nontoxic 

00007219 

Acceptable 
Page 48 of 80

Study Type Species 

Test 

material 

(% ai) 

Toxicity Toxicity 

Classification MRID & Status 

98 LC50: >5620 ppm Practically 

nontoxic 

00144304 

Acceptable 

1

 Toxicity values based on parent compound (TGAI). 

2 This study was reviewed twice, once in 1980 when it was classified as “Acceptable” and a second time in 1987 

when it was classified as “Supplemental”. The Supplemental classification was due to the presence of regurgitation 

in the two highest doses. 

Terrestrial Mammals-Chlorinated Isocyanurates

The chlorinated isocyanurates are slightly toxic to mammals on an acute basis (LD50 = 787 to 

868 mg/kg-bw; MRID 00150959 (see Appendix B)). Developmental and reproductive toxicity is 

not expected from exposure to the degradate, isocyanuric acid (see Appendix B). In reproductive 

toxicity testing with rats, isocyanuric acid produced no reported reproductive or fertility effects 

in offspring of any generation at doses up to and including a limit dose of 1000 mg/kg-bw/day 

(MRID #00150286). In one study with monosodium isocyanurate in rabbits (MRID 

#42054101), increased fetal and litter incidence of hydrocephaly was observed in offspring at a 

dose of 500 mg/kg-bw/day, a dose which was not maternally toxic. 

Nontarget Terrestrial Insects-Chlorinated Isocyanurates

Data are not expected to be required for the chlorinated isocyanurate uses because exposure is 

unlikely given the use pattern and fate of the chlorinated isocyanurates and their degradates. 

Aquatic - Fish and Invertebrate Toxicity-Chlorinated Isocyanurates/Chlorine

In addition to the chlorinated isocyanurate ecotoxicity data discussed here, additional chlorine 

toxicity information was obtained from the EPA Office of Water’s Ambient Water Quality 

Criteria for Chlorine - 1984 (EPA 1985). The document contains a review of public literature 

on effects of chlorine and based on the data derives freshwater and saltwater organism acute and 

chronic water quality criteria as total chlorine residual (TRC) for freshwater and chlorineproduced oxidants (CPO) for seawater. Current ambient water quality criteria for freshwater 

TRC and seawater CPO are based on the data in the 1984 document and the method for deriving 

water quality standards discussed in a 1986 Water Quality Document (USEPA, 1986). 

 Freshwater Criterion Maximum Concentration = 19 μg/L; 

 Freshwater Criterion Continuous Concentration = 11 μg/L; 

 Saltwater Criterion Maximum Concentration = 13 μg/L; and 

 Saltwater Criterion Continuous Concentration = 7.5 μg/L 
Page 49 of 80

According to the Office of Water’s Ambient Water Quality Criteria for Chlorine – 1984

(AWQC, EPA 1985), the term “total residual chlorine” (TRC) refers to the sum of free and 

combined chlorine in fresh water. In saltwater, in which chlorine will react with bromide, 

“chlorine-produced oxidants” (CPO) is used to refer to the sum of the free and combined 

chlorine and bromine oxidative products. Therefore, the toxicity values presented in the AWQC 

document, expressed as μg/L, refer to TRC for freshwater organisms and CPO for saltwater 

organisms.

Acute toxicity data on chlorinated isocyanurates for freshwater and saltwater fish and 

invertebrates are presented below. However, unlike the AWQC document unless specified 

otherwise in the tables, there data are expressed as ug ai/L, and not as TRC or CPO. 

Additionally, while these studies are marked acceptable, they were conducted under static 

conditions rather than flow-through and are based on nominal rather than measured 

concentrations. For purposes of a hazard assessment, they were considered acceptable. For 

assessment of risk tests using flow-through, measured concentrations from the AWQC Chlorine 

document are used.

Freshwater Fish

To assess potential acute and chronic risks to aquatic freshwater fish, acute and chronic effects 

data for chlorinated isocyanurates are used. The preferred test species are rainbow trout 

(Oncorhynchus mykiss), a coldwater species, and bluegill sunfish (Lepomis macrochirus), a 

warmwater species. Acute toxicity data for freshwater fish and invertebrates are available for 

trichloro-s-triazinetrione (Table 17), sodium dichloro-s-triazinetrione (Table 18), and sodium 

dichloroisocyanurate dihydrate (1 While these studies are deemed acceptable, they were 

conducted under static conditions rather than flow-through and are based on nominal rather than 

measured concentrations. For purposes of a hazard assessment, they are considered acceptable. 

Table 19). The 11 high purity grade test material studies (>90% ai) available for trout and 

bluegill categorize the three chlorinated isocyanurates tested as being very highly toxic to 

moderately toxic to freshwater fish (LC50’s = 80 to 1720 μg ai/L). As discussed previously these 

studies were conducted under static conditions and, given the test material rapid reactivity and 

dissipation, likely underestimate toxicity as compared to flow-through conditions. However, 

with the availability of chlorine toxicity studies from the AWQC documents no additional acute 

or chronic data are anticipated to be required. 

Freshwater Invertebrates

To assess potential acute and chronic risks to aquatic freshwater invertebrates. The preferred test 

species is Daphnia magna or Daphnia pulex acute and chronic effects data chlorinated 

isocyanurates are anticipated to be used. Five acute studies with high purity grade test material 

(>90% ai) have been submitted. The data categorize the three chlorinated isocyanurates tested as 

being highly toxic to freshwater invertebrates (LC50’s = 110 to 800 μg ai/L). As discussed 
Page 50 of 80

previously these studies were conducted under static conditions and, given the test material rapid 

reactivity and dissipation, likely underestimate toxicity as compared to flow-through conditions. 

However, with the availability of chlorine toxicity studies from the AWQC documents no 

additional acute or chronic data are anticipated to be required for chlorinated isocyanurates . 

Estuarine and Marine Fish and Invertebrates-Chlorinated Isocyanurates/Chlorine

TGAI data are required to assess acute and chronic risks to estuarine/marine fish and 

invertebrates potentially exposed from use of chlorinated isocyanurates in industrial processes 

and water systems. Acute testing with one fish, one shrimp (Mysidae or Penaeidae), and one 

mollusk are used. The preferred test species are the Silverside spp., Eastern oyster (Crassostrea 

virginica), and mysid shrimp (Americamysis bahia formerly called Mysidopsis bahia). No data 

have been submitted for the TGAI. Data submitted to support sodium hypochlorite, which also 

generates hypochlorous acid, indicate that hypochlorous acid (11.43-12.96% ai) is highly to very 

highly toxic to estuarine/marine fish (LC50’s = 50 and 380 μg ai/L) and invertebrates (LC50’s = 

160 and 200 μg ai/L). Those data were generated using sodium hypochlorite formulations and 

do not support the TGAI. However, data are available in the AWQC (EPA 1985) indicating that 

CPO is highly to very highly toxic to estuarine/marine fish and invertebrates (Table 17). No 

additional acute or chronic data for fish and invertebrates are anticipated as required. 

Table 17 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate 

Ecotoxicity Studies for Trichloro-s-triazinetrione 

Study Type Species 

Test 

material 

(% ai) 

Toxicity Toxicity 

Classification MRID & Status 

Acute – 

Freshwater Fish 

850.1075 

Rainbow trout 

100 96-hr LC50: 330 μg ai/L Highly toxic 00026195 

Acceptable1

100 96-hr LC50: 370 μg ai/L Highly toxic 00026193 

Acceptable1

92 96-hr LC50: 80 μg ai/L Very highly 

toxic 

00150966 

Acceptable1

Bluegill 

92 96-hr LC50: 200 μg ai/L Highly toxic 00150965 

Supplemental 

100 96-hr LC50: 620 μg ai/L Highly toxic 00026194 

Supplemental 

Acute – 

Freshwater 

Invertebrate 

850.1010 

Waterflea 

92.8 48-hr EC50: 170 μg ai/L Highly toxic 00150867 

Acceptable1

100 48-hr EC50: 800 μg ai/L Highly toxic 00154329 

Acceptable1

98 48-hr EC50: 640 μg ai/L Highly toxic 00150967 

Acceptable1

NR 48-hr EC50: 250 μg ai/L Highly toxic 

00019766 & 

00019383 

Supplemental 
Page 51 of 80

1 While these studies are deemed acceptable, they were conducted under static conditions rather 

than flow-through and are based on nominal rather than measured concentrations. For purposes 

of a hazard assessment, they are considered acceptable. 

Table 18 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate 

Ecotoxicity Studies for Sodium Dichloro-s-Triazinetrione 

Study Type Species 

Test 

material 

(% ai) 

Toxicity Toxicity 

Classification MRID & Status 

Acute – 

Freshwater Fish 

850.1075 

Rainbow trout 

100 96-hr LC50: 358 μg ai/L Highly toxic 

McCann, 1976a 

(TN** 1038) 

Acceptable1

98.3 96-hr LC50: 250 μg ai/L Highly toxic 256739 

Acceptable1

63 96-hr LC50: 240 μg ai/L Highly toxic 00019523 

Supplemental 

Bluegill 

100 96-hr LC50: 810 μg ai/L Highly toxic 

McCann, 1971a (TN 

368) 

Supplemental 

63 96-hr LC50: 283 μg ai/L Highly toxic 

00019523 & 

00130832 

Supplemental 

57 96-hr LC50: 2400 μg/L Moderately 

toxic 

00026194 (McCann, 

1976b);TN 1030) 

Acceptable1

7 96-hr LC50: 9800 μg/L Moderately 

toxic 

00026192 (McCann, 

1971b; TN 361) 

Supplemental 

Acute – 

Freshwater 

Invertebrate 

850.1010 

Waterflea 

98 48-hr EC50: 110 μg ai/L Highly toxic 00154328 

Acceptable1

55.63 48-hr EC50: 199 μg ai/L Highly toxic 00007241 

Supplemental 

** TN = test number 

1 While these studies are deemed acceptable, they were conducted under static conditions rather 

than flow-through and are based on nominal rather than measured concentrations. For purposes 

of a hazard assessment, they are considered acceptable. 

Table 19 Available Acute Endpoints from Freshwater Fish and Aquatic Invertebrate 

Ecotoxicity Studies for Sodium Dichloroisocyanurate Dihydrate 

Study Type Species 

Test 

material 

(% ai) 

Toxicity Toxicity 

Classification MRID & Status 
Page 52 of 80

Study Type Species 

Test 

material 

(% ai) 

Toxicity Toxicity 

Classification MRID & Status 

Acute – 

Freshwater Fish 

850.1075 

Rainbow trout 

98 96-hr LC50: 250 μg ai/L Highly toxic 00150951 

Acceptable1

71/123 96-hr LC50: 620 μg/L Highly toxic 

McCann, 1975a (TN2

0800) 

Supplemental 

71/123 96-hr LC50: 655 μg/L Highly toxic 

McCann, 1975b (TN 

0799) 

Supplemental 

Bluegill 

98 96-hr LC50: 460μg ai/L Highly toxic 00150950 

Acceptable 

100 96-hr LC50: 1,720 μg ai/L Moderately 

toxic 

McCann, 1976c (TN 

1039) 

Acceptable1

Acute – 

Freshwater 

Invertebrate 

850.1010 

Waterflea 98.3 48-hr EC50: 280 μg ai/L Highly toxic 00150952 

Acceptable1

1 While these studies are deemed acceptable, they were conducted under static conditions rather 

than flow-through and are based on nominal rather than measured concentrations. For purposes 

of a hazard assessment, they are considered acceptable. 2 TN = test number 

3 Multi-ai formulation containing 71% sodium dichloro-s-triazinetrione dihydrate and 12% simazine. Toxicity result 

expressed as μg formulation/L. 

Aquatic Plants-Chlorinated Isocyanurates/Chlorine

Data on chlorinate isocyanurates or chlorine are anticipated to be required for one vascular 

species, Lemna sp. (OCSPP 850.4400), three algal species (OCSPP 850.4500), and 

cyanobacteria (OCSPP 850.4550) are used to assess risk to aquatic plants. No data for 

chlorinated isocyanurates have been submitted. However, there are data in the AWQC 

documents (1985, 1986) that adequately addresses effects for aquatic plants from chlorine so no 

additional testing of chlorinated isocyanurates are required. 

Isocyanuric acid Toxicity

Except for two subacute avian dietary studies with a salt of cyanuric acid, monosodium 

cyanurate, and an acute test with a freshwater invertebrate, D. magna, no effects data on 

cyanurate/isocyanuric acid has been submitted to the OPP for review in support of pesticide 

registration. The Agency recognizes that isocyanuric acid is an EPA high production volume8

(HPV) chemical for which a Screening Information Data Set (SIDS) Assessment Report was 

performed (OECD SIDS 1999 and IIAHC 2003). Values found in these sources have been listed 

in the table below and consist of freshwater fish and invertebrate and green algae data. While 

some critical elements of these studies are identified in the HPV SIDS files, there is insufficient 

 

8

 http://www.epa.gov/chemrtk/index.htm 
Page 53 of 80

information available on the studies for AD to review the studies for purposes of a risk 

assessment. ECOSAR v1.1 was used to estimate freshwater and estuarine/marine fish and 

invertebrate acute and chronic values and the median effect concentration (EC50) and maximum 

allowable toxicant concentration (MATC; geometric mean of the NOAEC and LOAEC) for 

green algae. These values are also listed in Table 21. Isocyanuric acid/cyanuric acid was not 

part of the training set for this model and sensitivity as compared to data in the HPV summaries 

indicates the potential for the model in this case to significantly overestimate sensitivity Data are 

anticipated to be required for one vascular aquatic plant species, Lemna sp. (OCSPP 850.4400), 

three algal species (OCSPP 850.4500), and cyanobacteria (OCSPP 850.4550). Acute and 

chronic freshwater and estuarine/marine fish and invertebrate data and seedling emergence and 

vegetative vigor. 

Table 20 Available Avian Acute Toxicity Studies for Isocyanuric Acid 

Study Type Species Test material 

(% Purity) Toxicity Toxicity Classification 

MRID & 

Status 

Acute – Avian 

Dietary 

850.2200 

Northern 

bobwhite 

Monosodium 

cyanurate 

90.8-92.3% 

LC50: >10,000 ppm Practically 

non-toxic 

00019604 

Acceptable 

Mallard 

Monosodium 

cyanurate 

90.8-92.3% 

LC50: >10,000 ppm Practically 

non-toxic 

00019605 

Acceptable 

Table 21 - Available Aquatic Organism data for Isocyanuric Acid 

Receptor 

Group 

Test 

Materiala Surrogate 

Species 

Risk 

Scenario Toxicity Endpoint Reference/ Study Classification 

Freshwater 

fish 

isocyanuric 

acid 

Generic fish Acute 96-h LC50 = 72.0 mg/L ECOSAR v1.1a

Rainbow trout Acute 96-h LC50 >2100 mg/Lb IIAHC 2004b

/ 

Unacceptablec

Bluegill Acute 96-h LC50 >1000 mg/Lb IIAHC 2004b

/ 

Unacceptablec

Fathead 

minnow Acute 96-h LC50 >1000 mg/Lb IIAHC 2004b

/ 

Unacceptablec

Japanese 

medaka Acute 96-h LC50 >100 mg/L OECD SIDS 1999/ 

Unacceptablec

Generic fish Chronic MATC = 1.85 mg/L ECOSAR v1.1a

Freshwater 

invertebrates 

isocyanuric 

acid 

Daphnid Acute 48-h EC50 = 24.6 mg/L ECOSAR v1.1a

Daphnid Chronic MATC = 1.49 mg/L ECOSAR v1.1a

D. magna Acute 48-hr EC50 >1000 mg/L 

(static test, nominal) 

MRID 00132442 

Supplemental 

Waterflea Acute 48-h EC50 = 1000 mg/Lb OECD SIDS 1999b

/ 

Unacceptablec Chronic NOEC = 65,900 μg/Lb

Estuarine/marine Isocyanuric Generic Acute 96-h LC50 = 46.9 mg/L ECOSAR v1.1a
Page 54 of 80

Receptor 

Group 

Test 

Materiala Surrogate 

Species 

Risk 

Scenario Toxicity Endpoint Reference/ Study Classification 

fish acid Generic Chronic MATC = 2.45 mg/L ECOSAR v1.1a

Estuarine/marine 

invertebrates 

Isocyanuric 

acid 

Mysid Acute 96-h LC50 = 6.98 mg/L ECOSAR v1.1a

Mysid Chronic MATC = 4.82 mg/L ECOSAR v1.1a

Algae isocyanuric 

acid Green algae 

EC50 96-h EC50 = 0.114 mg/L ECOSAR v1.1a

NOAEL MATC = 0.057 mg/L ECOSAR v1.1a

/ 

Acceptable Model 

EC50 96-h EC50 = 712 mg/Lb IIAHC 2004b

/ 

Unacceptablec

EC50 72-h EC50 = 620 mg/Lb OECD SIDS 1999b

/ 

Unacceptablec NOAEL 62.5 mg/Lb

MATC (maximum allowable toxicant concentration) = geometric mean of the NOEC and LOEC 

a ECOSAR v1.1 class specific estimations for aromatic triazines. Isocyanuric acid/cyanuric acid was not part of the 

training set for the ECOSAR model and values appear to potentially overestimate sensitivity. 

b

 While some critical elements of these studies are identified in the HPV SIDS files, there is insufficient information 

available on the studies for AD to review the studies for purposes of a risk assessment. These studies would need to 

be submitted for review by AD for incorporation in a risk assessment. 

c

 Study value is from a secondary source; the original study is not available. There is insufficient information 

available on the study to allow AD to conduct a review for determination of acceptability for use in a risk 

assessment. 

Appendix C REFERENCES 

Isocyanurate Industry Ad Hoc Committee, “Robust summaries for sodium dichloro-striazinetrione (CAS No. 2893-78-9) and sodium dichloro-s-triazinetrione dihydrate (CAS 

No. 51580-86-0)”, revised May 20, 2004. 

Isocyanurate Industry Ad Hoc Committee, “Robust summaries for trichloro-s-triazinetrione 

(CAS No. 87-90-1)”, revised May 20, 2004. 

McCann, J.A. 1971a. CDB-63 (Sodium dichloro-s-triazinetrione 100%): Toxicity to Bluegill: 

Test No. 368. (U.S. Environmental Protection Agency, Pesticides Regulation Div., 

Agricultural Research Center, Animal Biology Laboratory, unpublished report.) 

McCann, J.A. 1971b. Perf Perf Chlor (Sodium dichloro-s-triazinetrione 7%, Inert 93.7%): 

Toxicity to Bluegill: Test No. 361. (U.S. Environmental Protection Agency, Pesticides 

Regulation Div., Agricultural Research Center, Animal Biology Laboratory, unpublished 

report.) 

McCann, J.A. 1975a. Algimycin T (Sodium dichloro-s-triazinetrione dihydrate 71.5%; Simazine 

2-chloro-4, 6-bis ethylamino-s-triazine 12.0%; Inert 16.5%): Toxicity to Rainbow Trout|: 

Test No. 800. (U.S. Environmental Protection Agency, Pesticides Regulation Div., 

Agricultural Research Center, Animal Biology Laboratory, unpublished report.) 

McCann, J.A. 1975b. Algimycin T (Sodium dichloro-s-triazinetrione dihydrate 71.5%; Simazine 

2-chloro-4, 6-bis ethylamino-s-triazine 12.0%; Inert 16.5%): Toxicity to Rainbow Trout|: 
Page 55 of 80

Test No. 799. (U.S. Environmental Protection Agency, Pesticides Regulation Div., 

Agricultural Research Center, Animal Biology Laboratory, unpublished report.) 

McCann, J.A. 1976a. Cu-Chlor Concentrate (Sodium dichloro-s-triazinetrione 100%): Toxicity 

to Rainbow Trout|: Test No. 1038. (U.S. Environmental Protection Agency, Pesticides 

Regulation Div., Agricultural Research Center, Animal Biology Laboratory, unpublished 

report.) 

McCann, J.A. 1976b. Utiken Shock Treatment (Sodium dichloro-s-triazinetrione 57%, Inert 

43%): Toxicity to Bluegill|: Test No. 1030. (U.S. Environmental Protection Agency, 

Pesticides Regulation Div., Agricultural Research Center, Animal Biology Laboratory, 

unpublished report.) 

McCann, J.A. 1976c. Arco Super shock Granular (Sodium dichloro-s-triazinetrione 100%) 

Toxicity to Bluegill|: Test No. 1039. (U.S. Environmental Protection Agency, Pesticides 

Regulation Div., Agricultural Research Center, Animal Biology Laboratory, unpublished 

report.) 
Page 56 of 80

Appendix D: ECOSAR Version 1.1 Results Page for Isocyanuric Acid 

SMILES : N1C(=O)NC(=O)NC1(=O) 

CHEM : 1,3,5-Triazine-2,4,6(1H,3H,5H)-trione 

CAS Num: 000108-80-5 

ChemID1: 

MOL FOR: C3 H3 N3 O3 

MOL WT : 129.08 

Log Kow: 1.952 (EPISuite Kowwin v1.68 Estimate) 

Log Kow: (User Entered) 

Log Kow: (PhysProp DB exp value - for comparison only) 

Melt Pt: (User Entered for Wat Sol estimate) 

Melt Pt: 360.00 (deg C, PhysProp DB exp value for Wat Sol est) 

Wat Sol: 2.768 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

Wat Sol: (User Entered) 

Wat Sol: 2000 (mg/L, PhysProp DB exp value) 

 

 

-------------------------------------- 

Values used to Generate ECOSAR Profile 

-------------------------------------- 

Log Kow: 1.952 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 2000 (mg/L, PhysProp DB exp value) 

 

------------------------------------------------ 

Available Measured Data from ECOSAR Training Set 

------------------------------------------------ 

 No Data Available 

-------------------------------------- 

ECOSAR v1.1 Class-specific Estimations 

-------------------------------------- 

Triazines, Aromatic 

 Predicted 

ECOSAR Class Organism Duration End Pt mg/L (ppm) 

=========================== ================== ======== ====== ========== 

Triazines, Aromatic : Fish 96-hr LC50 72.039 

Triazines, Aromatic : Daphnid 48-hr LC50 34.650 

Triazines, Aromatic : Green Algae 96-hr EC50 0.114 

Triazines, Aromatic : Fish ChV 1.852 

Triazines, Aromatic : Daphnid ChV 1.491 

Triazines, Aromatic : Green Algae ChV 0.057 

Triazines, Aromatic : Fish (SW) 96-hr LC50 46.900 

Triazines, Aromatic : Mysid (SW) 96-hr LC50 6.987 

Triazines, Aromatic : Fish (SW) ChV 2.456 

Triazines, Aromatic : Mysid (SW) ChV 4.820 

=========================== ================== ======== ====== ========== 

Neutral Organic SAR : Fish 96-hr LC50 116.978 

(Baseline Toxicity) : Daphnid 48-hr LC50 61.332 

 : Green Algae 96-hr EC50 56.868 

 : Fish ChV 11.375 

 : Daphnid ChV 6.371 

 : Green Algae ChV 12.545 

 Note: * = asterisk designates: Chemical may not be soluble enough to 

 measure this predicted effect. If the effect level exceeds the 

 water solubility by 10X, typically no effects at saturation (NES) 

 are reported. 
Page 57 of 80

 

 

------------------------------ 

Class Specific LogKow Cut-Offs 

------------------------------ 

If the log Kow of the chemical is greater than the endpoint specific cut-offs 

presented below, then no effects at saturation are expected for those endpoints. 

 

Triazines, Aromatic: 

------------------- 

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

--------------------------------- 

Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) 

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

------------------------------------------------------------------------------ 
Page 58 of 80

Appendix E: Response to the 60-Day Public Comments on the Chlorinated 

Isocyanurates

The Office of Pesticide Programs' Antimicrobial Division (AD) has reviewed the public 

comments received concerning the Preliminary Work Plan (PWP) for the Chlorinated 

Isocyanurates Registration Review, Case# 0569 (Docket ID Number EPA- HQ- OPP- 2012- 

0794). 

Comments were received from the Isocyanurates Industry Ad Hoc Committee (IIAHC), a 

consortium (consortium number 55643) of 12 manufacturers worldwide of the chlorinated 

isocyanurates. The following are the responses to each one of IIAHC’s, comments in their letter 

dated February 11, 2013, which may be seen in the docket for this case: 

The first five comments were determined to be the most critical issues requiring a response per 

IIAHC letter. 

Comment 1. The PWP indicates in several places that the Agency needs to review several 

references cited in the HPV Summaries, which was produced and submitted to the EPA by the 

IIAHC. The PWP also cites other needs for data, particularly ecotox data (acute toxicity to fish, 

algae, fish juvenile growth, Daphnia magna reproduction) which the IIAHC or its individual 

members own. The IIAHC and members thereof also own several new studies (chironomid, 

earthworm, phyto-toxicity, skin sensitizer, physical/chemical properties, acute inhalation on 

isocyanuric acid, new Ames test, and others) not specifically requested by the PWP, but which 

could be of considerable interest to EPA’s review of the chlorinated isocyanurates. Further, 

twelve studies were submitted to the EPA in November, 2007. No DERs have been received to 

date, and the IIAHC believes that these studies, and the other studies mentioned above, should all 

be reviewed prior to the issuance of a DCI. 

The IIAHC would be happy to meet with the EPA and review any and all additional studies 

which the EPA might require for performing the Registration Review. The IIAHC and members 

thereof would be happy to submit those studies required by the EPA for the Registration Review. 

Agency's Response: Regarding studies submitted to the Agency in November, 2007, upon 

further review of the Agency’s files the following studies have been located, and will be 

reviewed prior to issuing any GDCI, and if found to be acceptable for use in a risk assessment 

will be used in lieu of modeled values, where appropriate. 

MRID Citation Reference 

47302305 Skin sensitization in the guinea pig – Magnusson and Kligman maximization 

method (NaDCC dihydrate). 

47302306 Vryenhoef, H.; Hill, J. (2007) Monosodium Salt of Cyanuric Acid: Navicula 

pelliculosa: Algal Inhibition Test. Project Number: 2255/0001. Unpublished 

study prepared by Safepharm Laboratories, Ltd. 52 p. 

47302307 Sewell, I.; Mullee, D. (2007) Monosodium Salt of Cyanuric Acid: Daphnia 
Page 59 of 80

MRID Citation Reference 

magna Reproduction Test. Project Number: 2255/0002. Unpublished study 

prepared by Safepharm Laboratories, Ltd. 70 p. 

47302308 Sewell, I.; Mullee, D. (2007) Monosodium Salt of Cyanuric Acid: Fish, Juvenile 

Growth Test - 28 Days. Project Number: 2255/0003. Unpublished study 

prepared by Safepharm Laboratories, Ltd. 63 p. 

47302309 Goodband, T.; Mullee, D. (2007) Monosodium Salt of Cyanuric Acid: SedimentWater Chironomid Toxicity Test Using Spiked Sediment. Project Number: 

2255/0004. Unpublished study prepared by Safepharm Laboratories, Ltd. 57 p. 

47302310 Goodband, T. (2007) Monosodium Salt of Cyanuric Acid: Acute Toxicity to 

Earthworms (Eisenia foetida). Project Number: 2255/0005. Unpublished study 

prepared by Safepharm Laboratories, Ltd. 35 p. 

47302311 Clarke, N. (2007) Monosodium Salt of Cyanuric Acid: Assessment of the 

Inhibitory Effect on the Respiration of Activated Sewage Sludge. Project 

Number: 2255/0006. Unpublished study prepared by Safepharm Laboratories, 

Ltd. 29 p. 

47302312 Cyanuric acid: Physical and chemical characteriscs: Partition coefficient (nOctanol/Water). 

41943101 Murphy, D.; Peters, G. (1991) Sodium o-Nitrophenolate: A 96-Hour FlowThrough Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss). 

Unpublished study prepared by Wildlife International, Ltd. 38 p. 

Comment 2. We do not agree with the conclusion that trichloro-s-triazinetrione or sodium 

dichloro-s-triazinetrione are dermal sensitizers. 

The study cited is MRID 00144720, J. Mappes, “Dermal sensitization test performed on Na 

trichloroisocyanurate”, Bioassay Systems Corp., Project 120066, Oct 1984. There are several 

issues with this study which indicate that the study may not be acceptable or that the stated 

conclusion is incorrect: 

 The 1987 DER concluded that it is a "very mild sensitizer." However, the original data 

review in 1984 by James Wilson of the EPA agreed with the study conclusion that it is not 

a sensitizer. 

 There were too few animals used in the study and the inductions and challenges occurred 

at different times than in the current protocol. A minimum of 20 treatment animals (versus 

10 in the Mappes study) is recommended for the Buehler method. This may have been a 

contributing factor to the equivocal nature of the response, which was borderline at worst. 

 The product was applied in a dry, pure form during the initial exposures and during the 

challenge. However, the study reported no irritation during the initial exposure, even 

though the product is a severe dermal irritant (when wet), see Table 13 of the PWP. A 

slight amount of moisture present during the challenge could have been the cause of the 

observed minor irritation. 

Performing a skin sensitization test with a severe dermal irritant is inherently difficult. The test 

substance should be tested at a concentration where it is not irritating. Plus, the severity of the 
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dermal irritation produced by either trichloro-s-triazinetrione or sodium dichloro-s-triazinetrione 

is strikingly different for dry product versus wet product, with wet material being much more 

irritating. 

More recent studies which fully meet EPA guidelines, on both trichloro-s-triazinetrione and 

sodium dichloro-s-triazinetrione dihydrate, have concluded that the product is not a sensitizer: 

 D. Allen, Safepharm Laboratories Ltd. (2000) ACL 90XG Chlorinating Composition: 

skin sensitization in the guinea pig - Magnusson and Kligman maximization method, 

Project 1402/006, 22 pp. 

 D. Allen, Safepharm Laboratories Ltd. (2000) ACL 90 Chlorinating Tablets: skin 

sensitization in the guinea pig - Magnusson and Kligman maximization method, Project 

1402/007, 22 pp. 

 D. Allen, Safepharm Laboratories Ltd. (2000) ACL 56G Chlorinating Composition: skin 

sensitization in the guinea pig - Magnusson and Kligman maximization method, Project 

1402/005, 22 pp. MRID 47202305 

These studies substantiate IIAHC’s recommendation that these chlorinated isocyanurates should 

not be classified as skin sensitizers. These IIAHC-owned studies were referenced in the HPV 

summaries. One has been submitted to the EPA. The IIAHC would be happy to discuss and 

submit the other two studies, as required. 

Agency's Response: The agency will review all available studies during registration review and 

use a weight of evidence approach to determine if the chlorinated isocyanurates are dermal 

sensitizers. The above mentioned studies should be submitted by IIAHC so they can be included 

in the review. 

Comment 3. Tables 1 and 8 are intended to summarize all of the data requirements. However, 

additional potential data requirements are scattered throughout the PWP and are not included in 

these summary tables. For example, in Appendix A, Page 36, the PWP indicates that the Agency 

needs to review several primary references cited in the HPV Summaries. However, Tables 1 and 

8 list some but not all of the required data. The Final Work Plan should clarify the anticipated 

data requirements. 

Also, pages 48-49 indicate that numerous aquatic toxicity data requirements, including chronic 

data (850.1400 Fish Early-Life Stage Toxicity Test for freshwater and for marine fish, 850.1300 

- Daphnid Chronic Toxicity Test for freshwater invertebrates, and 850.1350 - Mysid Chronic 

Toxicity Test for marine invertebrates), are anticipated to be required. However, these studies are 

not included in either Table 1 or Table 8. The Final Work Plan should specify whether such data 

are required or not. 

The IIAHC would like to meet with EPA to discuss and further clarify the data requirements. 
Page 61 of 80

Agency's Response: The chronic fish and aquatic invertebrate studies are anticipated to be 

required as indicated in Appendix C. Tables 1 and 8 have been revised to include those expected 

requirements. Additionally, Tables 1 and 8 have been revised to include any missing 

environmental fate requirements. 

Comment 4. It is clear that the ECOSAR v1.1 model used to estimate the toxicity endpoints for 

isocyanuric acid in Tables 11 and 21 provides values which are completely incompatible with the 

values from experimental studies. Despite this, the results from the model in Table 21 have been 

selected for use in Table 11 over the experimental data because EPA did not have copies of the 

studies. As noted above, the IIAHC is willing to submit any and all studies referenced in the 

HPV Summaries, if required. The IIAHC and members thereof also own additional test data 

which can be provided for Agency review. 

In contrast to the ECOSAR calculations, all of our ecotoxicity experimental data have shown that 

isocyanuric acid has very low toxicity to aquatic organisms. The PWP provides no details on 

how the ECOSAR calculation was accomplished. The results from the ECOSAR model should 

be dropped from the environmental risk assessments, as they do not provide any realistic 

estimate of the true toxicity of isocyanuric acid to aquatic organisms. 

Agency's Response: The difference in sensitivity between ECOSAR modeled data and HPV 

data has been noted in the document. The Agency will use submitted experimental ecotoxicity 

data, which upon review have been found to be “Acceptable” for use in a risk assessment9 over 

modeled ecotoxicity data (i.e., ECOSAR results). If the IIAHC or other interested parties are 

aware of experimental data that may be able to be used to replace the modeled values, these 

studies should be submitted for review and consideration in the risk assessment. The ECOSAR 

calculations are added as Appendix D. 

Comment 5. The re-entry level for swimming pools is given as 3 ppm chlorine. This is true for 

many labels, but some labels (EPA Reg. Nos. 1258-1338, 5185-100, 5185-144 and 88896-3) 

have recently been approved with a re-entry level of 4 ppm chlorine (“Reentry into treated 

swimming pools is prohibited above levels of 4 ppm chlorine due to risk of body injury.”). 

Furthermore, the EPA has agreed that a re-entry level of 4 ppm chlorine is acceptable at a 

November 16, 2011 meeting between representatives of the IIAHC and the OCSPP, 

Antimicrobial Division. The Final Work Plan should indicate that the acceptable re-entry level is 

4 ppm chlorine. 

Agency's Response: The ppm level for re-entry into swimming pools has been changed to 4ppm 

in the FWP. 

 

9 U.S. EPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. Office 

of Prevention, Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, D.C. January 23, 2004. 

Support Document 1: Study Classification used by EFED in Data Evaluation Records (DERs) 

http://www.epa.gov/oppfead1/endanger/consultation/ecorisk-overview.pdf
Page 62 of 80

AdditionalCommentsonthePWP

Comment 6. We are surprised that the PWP does not include a specific request for Nontarget 

Plant Protection Data, including 850.4225 Seedling Emergence Tier II and 850.4250 Vegetative 

Vigor Tier II, as these were required in the May 16, 2012 DCI for NaBr, due to its once-through 

industrial water systems uses. Existing labels for the chlorinated isocyanurates allow for similar 

uses. The IIAHC is currently performing such a study and would be willing to submit this data to 

the EPA, if EPA requires this data. 

Agency's Response: Seedling emergence data for semi-aquatic plants (850.4100, rice) might be 

useful for the risk assessment. However, the study is needed only if the risk quotient from any 

aquatic plant growth Tier II study (850.4400, 850.4500, or 850.4550) exceeds a level of concern 

for aquatic plants. The agency has updated Tables 1 and 8 to reflect this anticipated requirement. 

Vegetative vigor data (850.4150, rice) is expected to be required for uses in which spray drift or 

irrigation using contaminated water may be a concern. 

Comment 7. The second sentence states that five active ingredients are included in this case but 

they are not named or listed here. The five active ingredients appear to be four listed in Table 3 

and potassium dichloro-s- triazinetrione, as mentioned in paragraph 2 on page 7. 

Agency's Response: The Case Overview has been updated to reflect that there are 3 active 

ingredients which have product registrations for chlorinated isocyanurates. 

Comment 8. The third sentence incorrectly states that potassium dichloro-s-triazinetrione was 

never registered by EPA in any pesticide products. In fact, EPA Reg. No. 524-105 was 

registered from 1975 to 1993. 

Agency's Response: The Agency acknowledges this fact and has made the correction to the 

FWP. 

Comment 9. The entry for the Available Chlorine content for trichloro-s-triazinetrione is 

questionable. We suggest that the range for products containing 99% or more trichloro-striazinetrione should be 89.5 - 91.5%. 

Agency's Response: The Agency concurs and the appropriate change has been made to Table 3 

in the FWP. 

Comment 10. (a)The first line of Table 4 (four instances) mistakenly refers to Table 1 for 

product identity and composition. These references actually refer to Table 3. (b) Table 4 does 

not identify the source/date of the information provided. This document, as with others in the 

past, will be used as a reference source and it is essential to document the source of data. (c)

The IIAHC has recently generated new GLP data for several physical/chemical properties of 

trichloro-s- triazinetrione, sodium dichloro-s-triazinetrione and sodium dichloro-s-triazinetrione 
Page 63 of 80

dihydrate, including better values for pH, melting point, density and solubility in water. The 

IIAHC would be willing to submit the relevant studies, if required. 

Agency's Response: (a) The Agency concurs with these comments and the FWP has been 

changed accordingly. 

(b) The agency concurs with these comments and the FWP has been changed to insert the source 

of data, 1988 Registration Standard and 1992 RED. 

(c) The IIAHC should submit the above mentioned studies be submitted so they can be included 

in the review. 

Comment 11. Table 5 indicates that there are two active products based on dichloro-striazinetrione. To the best of our knowledge, no company currently sells a product based on 

dichloro-s-triazinetrione and no manufacturer has a Manufacturing Use label registered for 

dichloro-s-triazinetrione. 

NPIRS lists two products under PC Code 081401: 5185-497 (Bio-Lab Wonder Tab) and 6466-

12 (Fitzpatrick Bros. Kitchen Klenzer). However, 5185-497 is improperly classified in NPIRS as 

the label indicates that this product contains 66.7% sodium dichloro-s-triazinetrione (PC Code 

081404), not dichloro-s-triazinetrione. BioLab (IIAHC member) confirms that 5185-497 

contains sodium dichloro-s- triazinetrione. NPIRS does not list a product containing 99.7% 

dichloro-s-triazinetrione. Fitzpatrick Bros. has confirmed that 6466-12 (Kitchen Klenzer, last 

label revision 2003) actually contains 0.8% sodium dichloro-s-triazinetrione, not dichloro-striazinetrione, therefore, this product is mislabeled. 

Agency's Response: The FWP has been updated to reflect that only three active ingredients are 

contained in registered pesticides and are to be assessed in Case 5069: sodium dichloro-striazinetrione (PC Code: 081404); trichloro-s-triazinetrione (PC Code: 081405); and sodium 

dichloro-s-triazinetrione dihydrate (PC Code: 081407). 

Comment 12. Table 5 indicates that some formulations are liquids or liquid-solutions. Liquid 

formulations of the chlorinated isocyanurates are not sufficiently stable to package and market as 

finished products. Therefore, we believe that all of the formulations listed in Table 5 as Liquid 

formulations or Liquid- solutions are misclassified. Although the NPIRS database lists a number 

of products classified as “solutions-ready to use”, these products are all actually solid 

formulations (e.g., tablets or granules). 

EPA currently defines formulations based on standard agricultural pesticide terminology. This 

can cause confusion for antimicrobial formulations, which have inherently different physical 

properties and use patterns than the agricultural pesticide formulations. This is especially true 

for solid formulations, as the agricultural pesticide terminology implies certain properties which 

normally do not apply to the antimicrobial formulations. In particular for Table 5, for 

agricultural pesticide formulations “wettable powders” are dry, finely ground solids that are 

usually mixed with water to form a suspension for application as a spray. In many cases, the 
Page 64 of 80

product has very low solubility in water. In contrast, trichlor-s-triazinetrione, sodium dichloro-striazinetrione and sodium dichloro-s-triazinetrione dihydrate powders are “soluble powders”, that 

is, they are fully soluble in water. They are either added directly to the water system, where they 

dissolve completely, or are pre-dissolved in water and then added to the water system. 

Agency's Response: The Agency concurs with this comment and the FWP has been changed to 

indicate that the wettable powders are actually soluble powders and that no liquid formulations 

are registered. 

Comment 13. The IIAHC requests a copy of the full list of chlorinated isocyanurate 

products/uses derived from labels which was recently prepared by EPA’s contractor. This list 

would be very useful in several situations for our understanding of the Work Plan. 

Agency's Response: This information could be obtained through a Freedom of Information Act 

(FOIA) request. 

Comment 14. The 600 ppm Maximum Application Rate listed for the Drinking Water use site is 

incorrect. The correct value is 500 ppm. 

Agency's Response: The Agency concurs with this comment and the FWP has been changed 

accordingly. 

Comment 15. Page 10, Table 6 – This corresponds to comment #5 in this response to comments 

appendix (See Critical Issue #5). 

Agency's Response: The Agency concurs with this comment and the FWP has been updated. 

Comment 16. To the best of our knowledge, no company currently sells a product based on 

dichloro-s-triazinetrione. 

Agency's Response: The Agency concurs with this comment and the FWP has been updated. 

Comment 17. There are four instances where “sodium dichloro-s-triazinetrione dihydrate” is 

incorrectly written as “dichloro-s-triazinetrione dihydrate”. 

Agency's Response: The Agency concurs with this comment and the FWP has been updated. 

Comment 18. There is one instance where “sodium dichloro-s-triazinetrione” is incorrectly 

written as “dichloro-s- triazinetrione”. 

See comment above on Table 5 concerning liquid formulations. We believe that all formulations 

classified as “ready-to-use solutions” are inaccurate. 

See comment above on Table 5 concerning agricultural pesticide terminology. The PWP 

indicates that some chlorinated isocyanurate formulations are “water dispersible granules”. For 

agricultural pesticide formulations, “water dispersible granules” normally comprise a small 

percentage of active ingredient adsorbed onto an inert carrier. Water dispersible granules must be 
Page 65 of 80

mixed with water, where the granules break apart into fine particles, forming a suspension or 

slurry, which is then applied by spraying. This suspension requires constant agitation to keep the 

particles suspended in water. In contrast, trichlor-s-triazinetrione, sodium dichloro-striazinetrione and sodium dichloro-s-triazinetrione dihydrate granules are “soluble granules”, that 

is, they are fully soluble in water. They are either added directly to the water system, where they 

dissolve completely, or are pre-dissolved in water and then added to the water system. We do 

not know of any chlorinated isocyanurate formulation where the active ingredient is adsorbed 

onto a granular carrier. Therefore, we believe that “water dispersible granules” is not an accurate 

formulation type descriptor for any chlorinated isocyanurate product. 

Agency's Response: The Agency concurs with this comment and the FWP has been updated. 

Comment 19. SRI International, “Chlorinated isocyanurates”, Chemical Economics Handbook, 

Feb 2012 (page 14) provides more recent information on the estimated U.S. consumption than 

the 2006 Kline report. It estimated that the U.S. consumption in 2011 was less than 4% higher 

than in 2004. 

Agency's Response: The agency concurs with these comments and the FWP be changed 

accordingly. 

Comment 20. In the second sentence, “dehydrate” is incorrect. The correct term is “dihydrate”. 

Agency's Response: The agency concurs with this comment and the FWP has been updated. 

Comment 21. In the 3rd sentence, “such transient” should be “such as transient”. 

Agency's Response: The agency concurs with this comment and the FWP has been updated. 

Comment 22. In the 3rd sentence, “such chemical burns” should be “such as chemical burns”. 

In the 4th sentence, “should be not be” is more correctly written as “should not be”. 

Agency's Response: The agency concurs with this comment and the FWP has been updated. 

Comment 23. “Sodium dichloro-isocyanurate hydrate” is incorrect. The correct name is 

“Sodium dichloro- isocyanurate dihydrate”. 

Agency's Response: The agency concurs with this comment and the FWP has been updated. 

Comment 23b. If there are no dichloro-s-triazinetrione products on the market, the dichloros-triazinetrione incidents are probably not listed properly. 

Agency's Response: The agency concurs with this comment and the FWP has been updated. 

Comment 24. Page 15, Table 8, Indoor Exposure, Inhalation and Page 6, Table 1 

Table 8 indicates that the test substance for the required indoor exposure studies should be the 

TGAI. However, the exposure studies already performed by the AEATF or currently being 
Page 66 of 80

planned by the AEATF normally use a surrogate compound to minimize risk to the human test 

subjects. For example, the mop study (MRID 48210201) with its supplement (MRID 48724801) 

used DDAC as the test substance. The Final Work Plan should clearly state that the use of a 

surrogate compounds in the exposure studies will be acceptable. 

Agency's Response: The Agency concurs with this comment and the FWP has been updated. 

Comment 25. There is no data requirement for dermal exposure data, even though the AEATF 

studies contain such data, and such data are relevant to an informed risk assessment. 

Agency's Response: The Agency does not concur with this comment at this time. Although 

dermal points of departure (PODs) for systemic effects were selected as listed in Table 9 of the 

PWP, these PODs are from oral exposure studies and when adjusted for dermal absorption yield 

dermal equivalent PODs of greater than 1000 mg/kg/day. This means that systemic dermal 

toxicity is very low and does not need to be assessed. Dermal irritation may need to be 

addressed because acute tests indicate Tox I. 

Comment 26. Page 15, Table 8, Residential Post Application, Disinfected Floors, Incidental 

Oral Exposure and Page 6, Table 1 

OCSPP GLN 875.2300 is not listed on the EPA website for EPA test methods. It only exists in 

draft form. 

The chlorinated isocyanurates provide available chlorine, therefore, these would only be used on 

hard surface flooring, such as vinyl tile or ceramic tile. These products would not be used on 

carpets, since the carpets would potentially be bleached and thus permanently discolored. The 

Final Work Plan should clarify that the desired Indoor Surface Residue Dissipation data is for 

hard surface flooring only. The IIAHC is willing to work with EPA on clarifying label language, 

if needed. 

Simple worst-case calculations can be used and would indicate minimal exposure from 

disinfected floors, much less than the expected exposure from other uses such as swimming 

pools or drinking water. Would a worst-case calculation fulfill this data requirement? 

Agency's Response: The Agency concurs with these comments and is aware that the guideline 

exists only in draft form and will assist in the development of study protocols. The Agency will 

also consider exposure calculations submitted as waiver requests and determine their impact on 

whether data are need or not. 

The FWP has been changed to indicate that the Surface Residue Study is only needed for hard 

surface flooring only. 

Comment 27. For clarity, all abbreviations should be explained when first used. In Footnote 6, 

“DtD” means “Down the Drain”. 
Page 67 of 80

Agency's Response: The Agency concurs with this comment and the FWP has been updated. 

Comment 28. Footnote 7 to Table 8 indicates that some uses may be eligible for data waiver if 

Selenastrum capricornutum NOAEC results are greater than 1 ppm. The HPV Summaries 

included a study (T. Hollister (1978) Acute Toxicity of Cyanuric Acid (BN-78-1384330-1) to the 

Fresh-Water Alga Selenastrum capricornutum; EG&G Bionomics, Report No. BP-78-9-137; 

Study No. H74-500) which found that the 96 hr NOAEC for Selenastrum capricornutum was 

greater than 100 ppm. This study is owned by Occidental Chemical Corp. (IIAHC member) but 

has not been submitted to the EPA. Shikoku International Corp. (IIAHC member) also owns 

data on algae which also shows that the NOAEC is greater than 100 ppm. 

The IIAHC also has algal (Navicula pelliculosa and Skeletonema costatum, a marine algae) 

toxicity data on the monosodium salt of isocyanuric acid. We would be happy to submit these 

studies, if required. 

Agency's Response: The agency will review the Selanastrum study when it is submitted by 

IIAHC to fulfill the anticipated data requirement in Table 8. Results from that study, if 

acceptable, will determine if the additional waiver is accepted. A waiver request for the other 

plant data may be submitted at the same time, based on the >1 ppm results. 

Comment 29. A petition submitted to the U.S. FDA by Occidental Chemical Corp. (IIAHC 

member) calculated the potential human exposure to isocyanuric acid due to use of a sodium 

dichloro-s-triazinetrione based product in pulp/paper slimicide use. Using worst case 

assumptions, the estimated daily intake of isocyanuric acid was considerably lower than the 

chronic RfD in Table 9. Based on these results and other data submitted, FDA approved this 

product (EPA Reg. No. 935-71) for this use. See Food Contact Substance Notification (FCN) 

000495, effective June 18, 2005. FCN’s are listed on the FDA’s website at: 

http://www.fda.gov/Food/FoodIngredientsPackaging/FoodContactSubstancesFCS/ucm116567.ht

m. 

Use of the chlorinated isocyanurates for preservation of adhesives is on EPA Reg. No. 935-71 

only. This product has not been approved by the FDA for preservation of food-contact adhesives. 

As use for food-contact adhesives is not contemplated, the requested data on this use should not 

be required. 

Agency's Response: Regarding the pulp and paper slimicide use, EPA is required to conduct 

aggregate risk assessments which essentially combine all sources of exposure to all pesticides 

that have cyanuric acid/isocyanuric acid as a degradate including food, drinking water, 

residential, FDA-regulated uses, etc. The risk due to one chlorinated isocyanurate used as a 

slimicide cannot be considered in isolation. However, if actual residue data were submitted to 

FDA, the same data should be submitted to EPA as should the approach used to estimate dietary 

intake. 
Page 68 of 80

Regarding adhesive preservation, as the use appears on a FIFRA-approved pesticide label, it is 

the agency’s position that either the associated risk must be included in the aggregate risk or the 

label should be revised to state that the adhesive preservation use is for nonfood contact only. 

Comment 30.The HIARC report (2001) does not appear to be publically available. The IIAHC 

requests a copy for review. 

Agency's Response: The HIARC report (2001) will be placed in the docket at EPA-HQ-OPP2012-0794. 

Comment 31. For clarity, all abbreviations should be explained when first used. For example, 

UF = uncertainty factor and RfD = reference dose. (see http://www.epa.gov/risk/doseresponse.htm) 

Table 9 does not reference the original reports for the data, but refers to the HIARC report, 

which does not appear to be publically available. Since it is unclear which reports Table 9 refers 

to, it is difficult to comment on some of the conclusions in the Table. 

Two entries in Table 9 incorrectly reference a Developmental Toxicity study with rats. 

Appendix B (page 44) indicates that this data is from D. Rodwell (1990) Teratology study in 

rabbits with monosodium isocyanurate, Springborn Laboratories Inc., Study 3222.1, MRID 

42054101, which was done on rabbits, not rats. This correction was made in T. McMahon, 

3/26/01, D270655 (cited in section 3.2.2). Another study on rats, MRID 105168, resulted in a 

higher NOAEL, so it is not relevant to a toxicology endpoint. 

Footnote A indicates that the endpoints in Table 9 are for isocyanuric acid. However, the last 

entry (Inhalation) in Table 9 is for the active ingredient (sodium dichloro-s-triazinetrione 

dihydrate). This data appears to be from G. Rusch, Bio/dynamics (1979) A four week inhalation 

toxicity study of sodium dichloro-s-triazinetrione dihydrate in the rat, Project No. 78-7154, 

MRID 28525, 97495 or 132438, which was referenced by T. McMahon, 3/26/01, D270655. 

Therefore, Footnote A is confusing as the inhalation endpoint is for a different material than 

isocyanuric acid. 

The IIAHC now has a four-hour acute inhalation study on isocyanuric acid, which found no 

deaths at 5.25 mg/L. The IIAHC is willing to submit this report, if required. 

Agency's Response: The agency concurs with the comments regarding Table 9 and has revised 

Table 9 as appropriate. 

Comment 32. The table indicates that the chronic RfD is 1.5 mg/kg/day, which is based on the 

NOAEL of 154 mg/kg/day from the 2-year rat study and an UF of 100. However, MRID 

44834403, which was submitted to the EPA, indicates that this value is overly conservative. In 

particular, this report indicates that the UF should be less than 100. The normal UF of 100 

comprises a factor of 10 for intra-human variation and a safety factor of 10 for extrapolating 
Page 69 of 80

from rat to human. However, this report concluded that for the specific effects seen in the 2-year 

rat study, the rat is more sensitive than humans. In particular, the rat is more susceptible to the 

formation and retention of urinary calculi, formed by precipitation of isocyanuric acid/sodium 

isocyanurate in the kidneys at high doses. The rat is inherently more susceptible than humans due 

to physiological differences. Therefore, the report concluded that a safety factor of 10 for 

interspecies extrapolation is unreasonable and should be reduced. 

The IIAHC recommends that the EPA reconsider the calculation of the chronic RfD, using a 

smaller UF than 100. 

Agency's Response: The Agency will reevaluate the toxicity database and endpoints during the 

risk assessment phase of registration review and will consider the findings of MRID 44834403 at 

that time. 

Comment 33. The reference to “PTAP” is incorrect. This should refer to isocyanuric acid. 

Agency's Response: The Agency concurs with this comment and the FWP has been updated. 

Comment 34. The last paragraph indicates that “residue chemistry data are expected to be 

needed to determine dietary exposure”. However, the exact nature of the needed data is not 

clearly identified in Table 1 or Table 8. The IIAHC would like to meet with the EPA to discuss 

what, if any, data will be required. 

Agency's Response: Tables 1 and 8 both have the following as does the text at 3.2.1: 

 Residue chemistry data are anticipated to be needed to determine dietary exposure to 

cyanuric acid/isocyanuric acid following sanitization of food contact surfaces of food 

processing plants (including dairies) and food-handling facilities (including public eating 

places). Protocol submission is recommended. The anticipated DCI will address this. 

 Migration of cyanuric acid/isocyanuric acid from preserved adhesive to food and from 

paper/paperboard to food following the slimicide use. The anticipated DCI will provide 

that a protocol must be submitted for EPA approval prior to initiating the study. 

Comment 35. The third sentence says that “Residue chemistry data are expected to be needed to 

determine dietary exposure to the stable degradates and tautomeric pair cyanuric acid and 

isocyanuric acid following ...”. This sentence implies that degradates other than isocyanuric 

acid/cyanuric acid will be evaluated. There are no other “degradates” other than isocyanuric 

acid/cyanuric acid. 

Agency's Response: The agency agrees that there are no other “degradates” other than 

isocyanuric acid/cyanuric acid. The sentence has been modified to “Residue chemistry data are 

expected to be needed to determine dietary exposure to the stable, tautomeric degradate pair of 

cyanuric acid and isocyanuric acid following...” to clarify Cyanuric acid and isocyanuric acid 

are meant to be described as being both stable degradates and a tautomeric pair.
Page 70 of 80

Comment 36. Section 3.2.2 Paragraph 1 states: “...contamination of drinking water by the 

degradate cyanurate/isocyanurate may occur as a result of discharge from paper and paperboard 

mills, down-the-drain from swimming pools or food-handling establishments, or run-off from 

livestock premises.” We disagree that these discharges lead to any significant contamination of 

drinking water. Many of these discharges will go through a WWTP before discharge to the 

environment and any surface water used for drinking water will be treated at a drinking water 

plant. Either process could remove most of the isocyanuric acid from the water. In addition, 

biodegradation of the isocyanuric acid after being released to the environment and the large 

dilution expected upon discharge would result in isocyanuric acid concentrations much lower 

than the concentrations resulting from direct treatment of drinking water. 

Furthermore, published data (L. Wise, E. Walters (1917) Isolation of CYA from soil, J of 

Agricultural Research, 10, 85-91) indicate that isocyanuric acid is formed by natural processes, 

resulting in a natural isocyanuric acid level in soil up to 6 ppm. Once treated and diluted, the 

discharges described above will result in average levels in soil and natural bodies of water much

lower than the natural level. 

Agency's Response: The Agency acknowledged in its Preliminary Work Plan (beginning on 

page 36) that, 

“An examination of the chemical structure, open literature from Science Direct (Anderson, 2002: 

Kontchou and Gschwind, 1999, Table 12) and a review of information in a Robust Summary in 

the HPV documentation (http://www.epa.gov/hpv/pubs/summaries/tricltrz/c14659re.pdf-, Table 

12) indicates that a high percentage (up to 100%) of cyanuric acid may be removed either by 

aerobic WWTPs using acclimated microorganisms or WWTPs using anaerobic conditions 

(acclimated or unacclimated microorganisms). The primary removal mechanism was attributed 

to mineralization because (1) there was no evidence of sorption to sludge based on the low log 

Kow (1.95) and water solubility (2,000 mg/L) and (2) the study authors reported the release of 

CO2 and NH3 or the incorporation of these substances into microbial biomass.” 

To be able to give merit to this claim of mineralization, the Agency would need to review and 

evaluate the primary references cited in the HPV documentation. These fate data correspond to 

anticipated data requirements listed in Table 8 and the IIAHC and its members are encouraged to 

submit this data for these requirements. 

If fate data submitted to meet these anticipated data requirements are found to be acceptable and 

support rapid mineralization, the agency would be able to agree with the commenter that postWWTP discharges from paper and paperboard mills and down-the-drain from swimming pools 

or food-handling establishments would not be expected to result in releases of cyanuric acid to 

surface water downstream of these establishments and there would be no potential for cyanuric 

acid to enter drinking water intakes downstream of these sources. For run-off from livestock 

premises that would not undergo wastewater treatment, however, additional evidence of removal 
Page 71 of 80

in the surface water environment such as that provided by the anaerobic aquatic and aerobic 

aquatic metabolism studies would be required to demonstrate that there would be no potential for 

surface water downstream of these locations to contain cyanuric acid that could enter drinking 

water intakes downstream of livestock premises. 

Depending on the outcome of the review and evaluation of the primary references cited in the 

HPV documentation and/or review of the necessary environmental fate data listed above, the 

need to reassess human dietary exposure to cyanuric acid will be determined. 

Comment 37. The PWP references a number of publications, without providing a full citation. 

For example, this section refers to “Dufour, 2006” but does not list this reference in section 8. 

The full citation is: 

A. Dufour, O. Evans, T. Behymer, R. Cantú (2006) Water ingestion during swimming activities 

in a pool: a pilot study, Journal of Water & Health, 4, 425-430. 

The Dufour results and other input indicate that previous calculations of exposure to isocyanuric 

acid in swimming pools (S. Mostaghimi, “Review of non-dietary exposure and risk assessment 

for cyanuric acid applied to swimming pools”, U.S. EPA Letter, DP No. D270656, Mar 26, 

2001.) may have overestimated the amount of water ingested while swimming. 

The second line on page 20 says “...assuming a chlorinated isocyanurate concentration of 55 

mg/liter...”. This is obviously incorrect and “chlorinated isocyanurate” should be “isocyanuric 

acid”. 

In paragraph 2, the last sentence discusses using the Dufour study, which “...could be used to 

back calculate chloroisocyanurate exposures for comparisons to the estimates derived from the 

SWIMODEL”. 

Here “chloroisocyanurate” should be “isocyanuric acid”. Also, it is not clear if EPA intends to 

conduct this comparison and what implications it may have on SWIMODEL if results are not 

consistent. 

The exposure calculation in SWIMODEL has been refined since 2001. We assume the Agency 

will use the most recent version (version 3) of SWIMODEL at 

http://www.epa.gov/oppad001/swimodel.htm for calculating potential swimmer exposures. 

Agency's Response: The Agency concurs with the comment regarding the Dufour study and the 

full citation for the study will be added to the reference list. 

The Agency concurs with comment regarding the second line on page 20 and the phrase 

“chlorinated isocyanurante concentration of 55 mg/liter” has been changed to “isocyanuric acid 

concentration of 55 mg/liter”. 

The Agency concurs with the comments regarding the SWIMODEL and will use the most recent 

version when calculating swimmer exposures. 
Page 72 of 80

Comment 38. Occupational and residential exposure data is being generated by the AEATF, 

with full cooperation of the EPA. It is important that the Work Plan and DCI requests for data be 

consistent with the studies being performed by the AEATF. We look forward to working with 

both EPA and the AEATF to produce the studies required. Some members of the IIAHC are also 

members of the AEATF and are actively working with the AEATF Protocol Committee to 

develop the protocol for the upcoming Pour Solid study. 

Table 10 indicates that the exposure scenario for ingestion of treated drinking water consider 

long term exposure. While this is true, remember that isocyanuric acid is rapidly eliminated from 

the body (elimination half-life is about 4 hr) and that it is not metabolized and does not 

accumulate. Thus, isocyanuric acid ingested during one day is essentially completely eliminated 

by the next day’s exposure so there are no cumulative effects from daily exposure. 

Agency's Response: The agency concurs with the comment regarding the AEATF exposure 

data that are under development. 

The title of Table 10 has been changed to “ORE Scenarios for the Chlorinated Isocyanurates” 

and that the “Ingestion of treated drinking water” scenario be deleted since it is not an ORE 

scenario. Note, however, that dietary exposure to cyanuric acid via drinking water is addressed 

at 3.2.2. 

Comment 39. We generally agree with the discussion here, however, a number of papers have 

been published recently which contain additional data on the biodegradation of isocyanuric acid. 

The IIAHC would be happy to submit a review and a reference list. 

Agency's Response: The Agency will review studies\information submitted by IIAHC for 

isocyanuric acid as part of Registration Review. 

Comment 40. What kind of model will be used for these calculations? We would like to know 

how the model determines what percentage of the isocyanuric acid in the WWTP influent is 

released to the surface water and sediment, the basis for this assumption, and how these data will 

be used in the risk assessments. This pathway triggers ecotoxicity and potentially additional 

environmental data needs with down-the-drain and sanitary drain system disposals if the 

substance is not fully degraded or consumed by the WWTP process. 

Agency's Response: The down-the-drain model will be used for the calculations of isocyanuric 

acid exposure to WWTPs. Specific model assumptions are provided in the Final Work Plan. 

Comment 41. The IIAHC and its members anticipate submitting additional environmental 

toxicity and ecological effects data to support the planned risk assessments. 

Agency's Response: The Agency will consider the studies when submitted by IIAHC. 

Comment 42. In sentence 10, “IIHAC” should have been written as “IIAHC”. 
Page 73 of 80

Agency's Response: The correction has been made to the FWP.

Comment 43. The Final Work Plan should make it clear that the environmental risk assessments 

will only be done on isocyanuric acid. 

Agency's Response: Added statement to Section 1.2 Overview Case regarding what the risk 

assessment will evaluate. Risks from both the chlorine residual and tautomer degradates need to 

be addressed. Where these risks have been previously assessed and updated methods, and new 

policies do not change exposure, effects, and risk conclusions, a new risk assessment will not be 

performed. 

Comment 44. The IIAHC has a number of ecotox studies which have been or could be 

submitted. These studies will be of better quality than most open literature studies identified 

through ECOTOX. 

Agency's Response: The agency will consider any relevant studies submitted by the IIAHC. Per 

OPP policy for Registration Review risk assessments, relevant open literature studies identified 

through ECOTOX also will be considered: 

www.epa.gov/pesticides/science/efed/policy/policy_guidance/team_authors/endangered_species

_reregistration_workgroup/esa_evaluation_open_literature.htm 

Comment 45. Most of the internet links provided in this section have been changed, for 

example: 

http://www.epa.gov/owow/tmdl/ is now 

http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/index.cfm. 

http://ofmpub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail?p_cause_group_name=CH 

LORINE is now 

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=27

7 (which indicates only 40 water bodies impaired by chlorine) 

Footnotes 6 and 7 - the web-pages given are no longer correct. The causes of impairment are 

listed at: 

http://iaspub.epa.gov/waters10/attains_nation_cy.control?p_report_type=T#causes_303d

The sections on organochlorine pesticides and chlorinated pesticides are not relevant to the 

chlorinated isocyanurates.

The IIAHC would like to discuss these issues to determine the extent of EPA’s concerns for 

impaired waters. 

Agency's Response: 1) (a) The first link has not changed and the agency tested the link and it 

leads to the correct page whereas the one suggested to take its place leads to an Error 404 page 

and the agency will keep the original link in the FWP. (b) The agency agrees the second link is 

no longer correct and has tested and replaced that link in the FWP with the one provided in the 
Page 74 of 80

comment. (c) The agency checked the links in footnotes 6 and 7 of Section 6.1.2 and these linked 

to the correct web site pages. The link provided by the commenter is a general impairment and 

TMDL page and was added to the first paragraph, third sentence of Section 6.1.2. 

2) The agency is open to discussion with regards to impaired waters. 

Comment 46. Regarding Section 6.1.5 additional information corresponds to comment #1 in this 

response to comment appendix. The IIAHC and members thereof will be providing additional 

data to assist EPA’s risk assessments, see Critical Issue #1. 

Agency's Response: The agency thanks IIAHC and its members for any additional information 

that will assist the agency in refining its risk assessment. (See the Agency’s response to 

Comment 1.) 

Comment 47. The text states that EPA has no environmental fate data on isocyanuric acid. 

Instead, EPA cites scientific literature cited by the HPV Summaries for environmental fate data 

on isocyanuric acid. IIAHC can provide copies of the references in the HPV Summaries. In 

addition, the IIAHC can provide many additional published papers on biodegradation of 

isocyanuric acid. 

Agency's Response: Tables 1 and 8 provide generic anticipated data requirements; it does not 

list specific studies. These tables have been updated to include all anticipated environmental fate 

data requirements. The IIAHC can choose to submit HPV studies or any other relevant source 

for those data listed in Table 12. The agency will review and consider any relevant studies 

submitted by the IIAHC. 

Comment 48. The PWP indicates that the Agency needs to review several primary references 

cited in the HPV Summaries. The IIAHC will be happy to submit these. Otherwise, the PWP 

does not specify exactly what data are required. 

The first partial paragraph refers to Section 5.1.2 which supposedly includes relevant data 

requirements; however, the PWP does not contain a section 5.1.2. 

Agency’s Response: The reference to Section 5.1.2 has been removed. The FWP has been 

updated to identify the type of fate data anticipated to be required (see Comment #47). If 

IIAHC submits studies that were referenced in HPV Summaries which meet these anticipated 

data needs, those data will be reviewed for use in the risk assessment. Alternatively, if IIAHC 

has access to other studies which would fulfill the anticipated data requirements, IIAHC should 

submit them for agency consideration. 

Comment 49. The MRID cited for the hydrolysis study by Hu is incorrect; the correct reference 

is MRID 00056478. Also, Footnote 2 is not the correct citation for the hydrolysis study. The 

correct citation is: 

 H. Hu (1981) Hydrolysis study of aqueous sodium salt solutions of 2,4,6-trihydroxy1,3,5-triazine. Princeton Chemical Research and Development Centre. MRID 00056478. 
Page 75 of 80

Agency's Response: There are two references for Hu, one is for the hydrolysis study and the 

other is for the photolysis study. The MRIDs and footnotes have been corrected in the FWP. 

Comment 50. The statement “In surface waters and wastewater streams, possible transformation 

products like chlorine, HOCl, ClO3- may be present...” is inconsistent with the three previous 

bullet points. 

Agency's Response: The Agency does not concur with the comment because some residual 

chlorine may still be present even though hypochlorite is highly reactive. 

Comment 51. The IIAHC has not submitted additional subchronic, chronic, developmental, 

mutagenicity, and metabolism studies to the EPA since the HIARC report in 2001. However, the 

IIAHC has recently obtained a new Ames test study, which was performed according to the 

current protocol. The results of the new study agree with previous results (no mutagenic effects), 

so the conclusions of the HIARC study are unchanged. The IIAHC is willing to submit this 

report, if required. 

Agency's Response: The Agency will review all available studies during registration review and 

use a weight of evidence approach to determine if the chlorinated isocyanurates are mutagenic. 

IIAHC should submit that the above mentioned study be submitted so it can be considered by the 

agency. 

Comment 52. It should be noted that the IIAHC has also submitted MRID 43819301 which 

investigated the friability of these products. This relates to the potential attrition of these 

products into inhalable size particles during transportation and handling. The study measured the 

percent by weight of product less than 11 microns in size and less than 53 microns in size after 

transportation or after vibration. 

For granular products, this study found that less than 0.1% by weight of the product is smaller 

than 11 microns and less than 0.2% by weight is smaller than 53 microns. Vibration of the 

granular products did not appear to make any difference in these percentages. For tablets which 

had undergone vibration, this study found that less than 0.2% by weight of the product is smaller 

than 11 microns and less than 0.6% by weight is smaller than 53 microns (in the inhalable size 

range). This study demonstrated that the products are not friable. Therefore, only a very small 

percentage of the product is small enough to be inhaled if the product was released into the air. 

We have also attempted an acute inhalation study on trichloro-s-triazinetrione particles in the 45 

- 75 micron size range. These particles could not be aerosolized sufficiently to conduct the test, 

so that even if the product is released to the air, only the very small percentage smaller than 

about 50 microns could be suspended in air. Thus, the potential for inhalation exposure to these 

products is limited to less than 1% by weight of the product. 
Page 76 of 80

Based on the physical form of these products, as defined by the studies cited above, the 

inhalation exposure to particles of toxicological concern and the consequent inhalation risk to 

these products are low. 

Agency's Response: The agency will consider this information during registration review in its 

effort to characterize inhalation exposures. 

Comment 53. IIAHC agrees with the rankings listed for eye irritation (Category I) and skin 

irritation (Category I) are correct, particularly for wet material. However, the study cited, MRID 

00019754 (B. Brett (1976) Acute Toxicity Studies with Brom-O-Rings, IBT No. 601-08105) is 

inappropriate for either endpoint. This formulation contains both trichloro-s-triazinetrione and 

another material which may affect the study results. Therefore, this study is not directly 

applicable to pure trichloro-s-triazinetrione. Furthermore, this study was performed by IBT 

(EPA does not accept studies from IBT) and was not run under GLP. 

The IIAHC recommends referencing the following study performed on pure trichloro-striazinetrione for Primary Eye Irritation: 

 G. Wnorowski, Product Safety Labs (1995) ACL-90, primary eye irritation, Project ID 

3450. MRID 43592601 

The IIAHC recommends referencing one of the following studies performed on pure trichloro-striazinetrione for Primary Skin Irritation: 

 J. Gargus, Hazleton Laboratories America (1984) Primary dermal irritation study in 

rabbits, trichloro- s-triazinetrione”, Project 2291-103. MRID 150961 (also see HPV 

Summary) 

 J. Lemen, Hazleton Laboratories (1988) Primary dermal irritation study in rabbits 

(Biocare 90), Project HLA 2514-102. MRID 40835803 

 R. Shapiro, Product Safety Labs (1990) EPA acute dermal irritation test, 

trichloroisocyanuric, Project T-292. MRID 42180404 

Agency's Response: The Agency will review all available studies during registration review and 

use a weight of evidence approach to determine the acute toxicity categories. RASSB will reevaluate MRID 00019754 and determine if it should still be used for this determination 

Comment 54. IIAHC does not agree with the conclusion that trichloro-s-triazinetrione or sodium 

dichloro-s-triazinetrione are dermal sensitizers, and recommend that this be corrected to “not 

sensitizers”. See Critical Issue #2. 

Agency's Response: The Agency will review all available studies during registration review and 

use a weight of evidence approach to determine if the chlorinated isocyanurates are dermal 

sensitizers. IIAHC should submit the above mentioned studies so they can be considered by the 

agency.
Page 77 of 80

Comment 55. The third sentence on page 45 defines “total chlorine residual” (TRC) for 

freshwater and “total residual oxidant” (TRO) for seawater while the first paragraph on page 48 

defines “total residual chlorine” (TRO) as the sum of free chlorine and combined chlorine in 

fresh water, and “chlorine-produced oxidants” (CPO) as the sum of the oxidative products in 

seawater. These definitions are inconsistent, even though both reference the same source 

document. It appears that “TRO” on page 48 should really be “TRC”. 

Agency's Response: The correction has been made in the FWP. 

Comment 56. Given the conceptual models in Figures 1-4, we are surprised that this review 

does not discuss terrestrial organisms (such as earthworms) or sediment organisms (such as 

chironomid). The IIAHC owns studies on the toxicity of isocyanuric acid to earthworms and 

chironomid. We would like to meet with the Agency and review the data which could be 

submitted, if required. 

In addition, this review does not cover terrestrial plants and the PWP does not include a request 

for Nontarget Plant Protection Data, including 850.4225 Seedling Emergence Tier II and 

850.4250 Vegetative Vigor Tier II. We are surprised that these studies are not required, as these 

were required in the May 16, 2012 DCI for NaBr, due to the once-through industrial water 

system uses for NaBr. The IIAHC is currently performing such a study and would be willing to 

submit this data, if required. 

Agency's Response: AD does not require earthworm toxicity studies and does not assess risk to 

earthworms. AD will consider any sediment-toxicity data that IIAHC wishes to submit for 

isocyanuric acid but, based on the physical/chemical information, the major exposure 

compartment is expected to be water rather than sediment and so sediment data are not 

anticipated as being required. AD assesses risk to “semi-aquatic”-terrestrial plants using 

vegetative vigor and seedling emergence studies on rice (see Agency’s response to Comment 6). 

Comment 57. What use causes exposure of birds to the chlorinated isocyanurates to be of 

concern? In contrast, page 47, last paragraph, indicates that there is no concern for exposure of 

insects to chlorinated isocyanurates. 

Agency's Response: The avian acute oral study is required for all antimicrobial pesticides to 

determine whether a label precautionary-hazards statement is needed for wildlife (see 40 CFR 

§156.85 Non-target organisms). If a use results in an antimicrobial and/or its major 

transformation product(s) reaching surface water or the terrestrial environment, then exposure 

and risk to wildlife via the dietary route is assessed. As discussed in Section 4.1, in the case of 

chlorinated isocyanurates, while several of the use patterns are expected to reach surface water, 

bioconcentration and therefore the dietary exposure route for wildlife is not considered an 

environmental concern which is why the conceptual models show this pathway as dashed lines. 

Testing with terrestrial insects (honey bee) is required for antimicrobial use patterns where 

exposure is likely such as applications to crops and wood-preservative uses. 
Page 78 of 80

Comment 58. Both Tables 15 and 16 have a Footnote 1, but no reference to the footnote. The 

footnote should refer to “Toxicity”, the heading in column 4, as was done in Table 14. 

Several MRIDs given in Tables 15 and 16 are not listed in NPIRS. The numbers listed are 

Accession Numbers, rather than MRIDs. The following tables list the proper MRIDs: 

Table 15 (sodium dichloro-s-triazinetrione dihydrate) 

Number listed Correct MRID

256739 acute - avian oral, Bobwhite* 150947

256739 acute - avian dietary, Bobwhite150949

256739 acute - avian dietary, Mallard 150948

* This is a duplicate of 150947 

Table 16 (sodium dichloro-s-triazinetrione) 

Number listed Correct MRID

254911 00144306

254910 00144305

254909 00144304

In addition, the three studies listed in Table 16 with Accession No. 256739 are duplicates of 

studies in Table 15 and are incorrectly listed. Accession No. 256739 was submitted by 3V 

Sigma S.P.A. (IIAHC member) which only performed avian toxicity studies on sodium 

dichloroisocyanurate dihydrate. 

Agency's Response: The footnote has been corrected. The duplicates in Table 16 has been 

removed, additional duplicates were found in these tables and also removed. Three studies for 

isocyanuric acid, two with birds and one with a freshwater invertebrate, were found and added to 

this appendix. 

Comment 59. At the end of the sentence, “there degradates” should be read as “their 

degradates”. 

Agency's Response: That correction has been made in the FWP. 

Comment 60. This heading should be “Aquatic - Fish and Invertebrate Toxicity” as this section 

covers not only freshwater fish and invertebrates but also estuarine and marine organisms. 

Agency's Response: That correction has been made in the FWP. 

Comment 61. This section indicates that chronic toxicity data for freshwater fish (guideline 

850.1400 Fish Early-Life Stage Toxicity Test) and freshwater invertebrates (guideline 850.1300 - 

Daphnid Chronic Toxicity Test) are anticipated to be required. However, it is not clear from the 

PWP whether chronic toxicity data on the active ingredient or on the degradate, isocyanuric acid, 

is required. We recommend that the required chronic data should be on the degradate, 

isocyanuric acid, as the acute data for the active ingredients already indicate very high toxicity. 
Page 79 of 80

The IIAHC owns a 28 day juvenile fish growth study and a Daphnia magna reproduction test on 

the monosodium salt of cyanuric acid, which will at least partially meet these requirements. 

These studies have been submitted to EPA, but have not been reviewed in conjunction with any 

action. 

We are not familiar with the TN numbers used here to refer to studies. 

Agency's Response: The Agency agrees that the chronic studies should be conducted using 

isocyanuric acid, and that will be stated in the FWP. Data indicated in response to comment #1 

will be reviewed before a DCI is issued. 

Comment 62. This section indicates that chronic toxicity data for marine fish (guideline 

850.1400 - Fish Early-Life Stage Toxicity Test) and marine invertebrates (guideline 850.1350 - 

Mysid Chronic Toxicity Test) are “anticipated to be required”. However, it is not clear from the 

PWP whether chronic data on the active ingredient or on the degradate, isocyanuric acid, are 

required. We recommend that the required chronic data should be on the degradate, isocyanuric 

acid, as the acute data for the active ingredients already indicate very high toxicity. 

Occidental Chemical Corp. (IIAHC member) owns data on the acute toxicity of isocyanuric acid 

and of sodium dichloro-s-triazinetrione to Inland Silversides (Menidia beryllina) and Mysid 

shrimp, which can be submitted, if required. Other IIAHC members may also have some relevant 

data. 

Agency's Response: See previous comment regarding the test material for chronic studies. 

Comment 63. The website given for HPV data, 

http://www.epa.gov/hpv/pubs/general/hpvchemdata.html, has been moved. The current web 

address for the HPV Challenge is http://www.epa.gov/chemrtk/index.htm. 

Agency's Response: That correction has been made in the FWP. 

Comment 64. On Page 51, Table 21 which corresponds to comment #4 in this response to 

comments appendix (See Critical Issue #4.) 

Agency's Response: See response to comment #4. The agency will use actual data in lieu of the 

ECOSAR calculations for isocyanuric acid if IIAHC submits acceptable studies for evaluation. 

Comment 65. The table has several references to “IIHAC 2003” which refers to the HPV 

Summaries for trichloro-s- triazinetrione, sodium dichloro-s-triazinetrione and sodium dichloros-triazinetrione dihydrate, but doesn’t provide a full reference. The full references are: 

 Isocyanurate Industry Ad Hoc Committee, “Robust summaries for sodium dichloro-striazinetrione (CAS No. 2893-78-9) and sodium dichloro-s-triazinetrione dihydrate (CAS 

No. 51580-86-0)”, revised May 20, 2004. 

 Isocyanurate Industry Ad Hoc Committee, “Robust summaries for trichloro-striazinetrione (CAS No. 87-90-1)”, revised May 20, 2004. 
Page 80 of 80

Note that the IIAHC did not submit a separate HPV Summary for isocyanuric acid; the data for 

isocyanuric acid was included in the HPV Summaries for the active ingredients. However, the 

HPV Information System (HPVIS) lists some of this data separately for 1,3,5-Triazine2,4,6(1H,3H,5H)-trione (isocyanuric acid, CAS Number 108-80-5) and for 1,3,5-Triazine2,4,6(1H,3H,5H)-trione, monosodium salt (monosodium isocyanurate, CAS Number 2624-17-1). 

The references in the table to “IIHAC 2003” should be to “IIAHC 2004”. “IIHAC” is incorrect 

and should be “IIAHC”, for the Isocyanurate Industry Ad Hoc Committee. They should refer to 

the revised HPV Summaries submitted in 2004, rather than the original submissions in 2003. 

Footnote c indicates that several studies in the HPV Summaries are not available to the EPA. The 

IIAHC is willing to submit these studies, including the acute toxicity studies on isocyanuric acid 

and rainbow trout (Salmo Gairdneri), fathead minnows (Pimephales promelas), bluegill sunfish 

(Lepomis macrochirus), and fresh-water algae (Selenastrum Capricornutum). 

The OECD SIDS 1999 summary provides the results of several other studies which have not 

been submitted to the EPA. The SIDS summary indicates that the Japanese medaka fish, water 

flea (Daphnia magna) and green algae (Selenastrum capricornutum) data were obtained by the 

Environment Agency of Japan based on OECD Test Guidelines and GLP. 

Agency's Response: The citations have been corrected and references added to the FWP. As 

indicated in previous responses to comments, the Agency will review any data submitted to 

fulfill anticipated data requirements. 

FIFRA Endangered Species Task Force (FESTF): FESTF provided a list of Member Companies 

that could rely on data submitted by the Task Force in their letter dated February 11, 2013. 

California Stormwater Quality Association: Commended the agency on their improved 

examination of surface water quality risks for chlorinated isocyanurates in their letter dated 

February 12, 2013. 

TriTAC: Commended the agency on their improved examination of surface water quality risks 

for chlorinated isocyanurates in their letter dated February 12, 2013. 

California Stormwater Quality Association: Commended the agency on their improved 

examination of surface water quality risks for chlorinated isocyanurates in their letter dated 

February 12, 2013. 

Physicians Committee for Responsible Medicine (PCRM): PCRM commended the Agency 

for their holistic approach to risk assessment.